Ninja Nerd Embryology Notes Complete

Last edited: 8/5/2021
12. DEVELOPMENT OF THE GIT PART 1

Development of the GIT Part 1 Medical Editor: Jan Camille Santico
OUTLINE II) EMBRYONIC FOLDING
I) TRILAMINAR DISC (A) SAGITTAL PLANE

II) EMBRYONIC FOLDING
III) REVIEW QUESTIONS
IV) REFRENCES
I) TRILAMINAR DISC
rd
At the 3 week of development, the embryo is a
trilaminar disc
o Made up ectoderm, mesoderm, and endoderm
Figure 2. Sagittal Plane of Embryo
Underneath the surface ectoderm is the neural tube and
notochord The sagittal view shows the cranial and caudal ends of
Flanking the notochord is the intraembryonic mesoderm, the gut tube
which can be divided into: During the 4th week of development, folding along the
o Paraxial mesoderm sagittal plane will form the cranial and caudal folds
o Intermediate mesoderm o The endoderm lining will expand outwards and fold
o Lateral plate mesoderm The gut tube can be divided into three parts:
 Somatic layer o Cranial – foregut
 Splanchnic layer o Middle – midgut
Underneath the mesoderm is the endoderm, which forms o Caudal – hindgut
the epithelial lining of the gastrointestinal organs, Mesoderm surrounds the gut tube
accessary organs, and glands o Mesoderm cells at the cranial end will help form the
Above the ectoderm is the amniotic sac pericardiac cavity and the heart
Below the endoderm is the yolk sac, which helps in the
Neural crest cells from the ectoderm layer will develop
synthesis of red blood cells
into important ganglia for the GIT (e.g. myenteric plexus)
o The yolk sac also secretes the extraembryonic
The yolk sac is connected to the midgut via the
mesoderm, which surrounds the yolk sac and
vitelline/omphalomesenteric duct
amniotic cavity
The two openings of the digestive tract are derived from
The somatic and splanchnic mesoderm develop a cavity areas of fusion between the ectoderm and endoderm (of
called the intraembryonic coelom, which allows the two the gut tube)
mesoderm layers to become continuous with the o The oropharyngeal membrane (foregut) will
extraembryonic mesoderm perforate to form the mouth
Eventually, the embryo will fold along the transverse and o The cloacal membrane (hindgut) will perforate to
sagittal plane form the urogenital tract and anus
By the 6th week of development, the vitelline duct will
obliterate, leaving the umbilical cord
o Meckel’s Diverticulum
 An outpouching of the small intestine
 Results from the failure of the vitelline duct to
obliterate, leaving behind a connection between
the midgut and the anterior abdominal wall
Also during the 6th week, the small intestines will form a
loop and herniate through the umbilical cord
o The developing organs within the abdominal cavity
push out the small intestines
During the 11th week, the abdominal cavity has increased
in size, so the intestinal loop is pulled back in
Figure 1. Trilaminar Disc o Omphalocele
 Results from the failure of the intestinal loop to
return inside the abdominal cavity
 Can be detected through fetal ultrasound or serum
alpha fetoprotein levels of the mother
Development of the GIT Part 1 EMBRYOLOGY: Note #1. 1 of 3

(B) TRANSVERSE PLANE (2) Retroperitoneal Organs
Retroperitoneal organs have no mesentery and are
located outside the peritoneum
Instead of visceral/parietal serosa, they have adventitia
o Dense, irregular fibrous connective tissue that
anchors retroperitoneal organs to the abdominal wall
o Does not provide mobility
Examples:
o Kidneys
o Adrenal glands
o Parts of the duodenum
(i) Primary Retroperitoneal Organs

• Organs which never had a mesentery
• Located posterior to the peritoneum
• Examples:
o Abdominal aorta
o Inferior vena cava
o Adrenal glands
o Kidneys
o Ureter
o Bladder
Figure 3. Transverse Plane of Embryo o Lower rectum
• The transverse plane shows a cross-section of the o Esophagus
embryo
(ii) Secondary Retroperitoneal Organs
• The endoderm will fold outwards and downwards. It will
get sucked in and pushed out, forming the vitelline duct • Organs with mesenteries that were obliterated
• The amniotic cavity starts folding down • Examples:
• The splanchnic mesoderm will surround the vitelline duct o 2nd, 3rd, and 4th parts of the duodenum
and yolk sac o Ascending colon
• The somatic mesoderm will line the inner walls of the o Descending colon
amniotic cavity o Head and body of the pancreas
• Once the vitelline duct obliterates, the two endoderm
folds can merge, forming a closed gut tube
o Gastroschisis
 The lateral folds fail to fuse, resulting in the
herniation of abdominal contents
 The herniated intestines are not covered in
peritoneum, which could irritate the abdominal
cavity
(1) Intraperitoneal Organs
The splanchnic mesoderm will surround the gut tube,
forming a part of the GI tract (submucosa up to visceral
peritoneum)
The somatic mesoderm will line the inner walls of the
abdominal cavity (parietal peritoneum)
The visceral and parietal peritoneum connect/meet at the Figure 5. Retroperitoneal Organs
mesenteries, a ligament which connects
organs/structures to the abdominal wall and provides
mobility
Any organ with a mesentery is considered intraperitoneal
Examples:
o Stomach
o Liver
o Spleen
o Transverse colon
Figure 4. Intraperitoneal Organs

2 of 3 EMBRYOLOGY: Note #12. Development of the GIT Part 1
1) Meckel’s diverticulum results from ____

a) Failure of the endodermal folds to fuse
b) Failure of the vitelline duct to form
c) Failure of the vitelline duct to regress
d) Failure of the intestinal loop to return inside the
abdominal cavity
2) Which structure secretes the extraembryonic

mesoderm?
a) Yolk sac
b) Amniotic sac
c) Notochord
d) Intraembryonic coelom
3) All of the following structures are intraperitoneal,

EXCEPT
a) Stomach
b) Jejunum
c) Transverse Colon
d) Ascending Colon
4) Which of the following statements is TRUE?

a) Omphalocele results from the failure of the lateral
endodermal folds to fuse
b) The liver is a retroperitoneal organ
c) The yolk sac is connected to the hindgut via the
vitelline duct.
d) Retroperitoneal organs are covered with adventitia
5) Which of the following is NOT a primary

retroperitoneal organ?
a) Adrenal gland
b) Pancreas
c) Bladder
d) Lower Rectum
CHECK YOUR ANSWERS
IV) REFRENCES
Development of the GIT Part 1 EMBRYOLOGY: Note #1. 3 of 3

13. DEVELOPMENT & EMBRYOLOGY OF THE GI TRACT P2

Development & Embryology of the GI Tract Part 2 Medical Editor: Jan Camille Santico
OUTLINE
I) MESENTERIES
II) FOREGUT
III) MIDGUT
IV) HINDGUT
V) REVIEW QUESTIONS
VI) REFERENCE (B) ROTATION OF MESOGASTRIUM
(1) The dorsal and ventral mesogastrium
I) MESENTERIES will rotate clockwise, with the foregut tube as the central
axis
(1) Origin o The ventral mesogastrium will give rise to the liver
o The dorsal mesogastrium will give rise to the spleen
The foregut tube is surrounded by visceral peritoneum,
while the inner abdominal cavity is lined by parietal Further rotation will bring the ventral mesogastrium to the
peritoneum right side and the dorsal mesogastrium to the left side
The foregut is attached/suspended to the abdominal wall o This explains why the liver is located on the right side
via two mesenteries: ventral and dorsal of the body, and the spleen is located on the left side
(2) Definitions (i) The ventral mesogastrium

(i) A mesentery will eventually develop into the lesser omentum, which is
made up of the:
is a double-layered serous membrane made up of simple o Hepatogastric ligament
squamous epithelial tissue o Hepatoduodenal ligament
o Underneath the serous layer is areolar connective
tissue (basal layer) (ii) The dorsal mesogastrium
o Mesentery is where blood vessels, lymphatic vessels, will eventually develop into the greater omentum, which
and nerves can pass through is made up of:
o Gastrophrenic ligament
o Gastrocolic ligament
o Gastrosplenic ligament
Figure 1. Mesentery
(ii) The dorsal mesogastrium

is the term referring to the mesentery connecting the
foregut to the dorsal abdominal wall
(iii) The ventral mesogastrium

is the term referring to the mesentery connecting the Figure 2. Rotation of the Mesenteries
foregut to the ventral abdominal wall
Development & Embryology of the GI Tract P2 EMBRYOLOGY: Note #1. 1 of 3

(C) GREATER & LESSER OMENTUM III) MIDGUT
The mesenteries/omentum are ligaments which help
This section will enumerate the midgut derivatives and
suspend the organs in the peritoneum
their corresponding vascular supply and mesentery.
o They are different from the ligaments which connect
The main vascular supply of the midgut derivatives is the
bone to bone.
superior mesenteric artery , which further branches
The greater and lesser omentum can be visualized into:
through a sagittal view of the abdominal cavity o Intestinal arteries
The greater omentum is attached to the greater curvature o Ileo-colic artery
of the stomach, and the lower omentum is attached to the o Right colic artery
lesser curvature o Middle colic artery
o Recall: The stomach (which is part of the foregut)
undergoes rotation) Table 2. Vascular Supply and Mesentery of Midgut Derivatives
The greater omentum hangs over the intestines and Midgut Vascular
Mesentery
doubles back up Derivative Supply
o The transverse mesocolon is a ligament anchoring Distal half of Intestinal a. Retroperitoneal; no
the transverse colon to the abdominal wall Duodenum mesentery
o When the greater omentum doubles back up, it fuses Intestinal a. Small bowel
with the transverse mesocolon mesentery
A part of the lesser omentum is attached to the stomach Jejunum Ligament of Treitz –
and proximal duodenum suspends the fourth
The epiploic foramen is a hole underneath the part of the
hepatoduodenal ligament which leads to the lesser sac duodenum
Intestinal a. Small bowel
Ileum
mesentery
Distal Ileum Ileo-colic a.
(at the ileo-
cecal
junction)
Ileo-colic a. Small bowel
Cecum mesentery; can be
retroperitoneal in
some
Appendix Ileo-colic a. Mesoappendix
Ascending Right colic a. Retroperitoneal; no
colon mesentery
Proximal 2/3 Middle colic a.
of the Transverse
Figure 3. Sagittal View of Ligaments Transverse mesocolon
colon
II) FOREGUT
This section will enumerate the foregut derivatives and
their corresponding vascular supply and mesentery. IV) HINDGUT
The main vascular supply of the foregut derivatives is the This section will enumerate the hindgut derivatives and
celiac trunk, which further branches into: their corresponding vascular supply and mesentery.
o Left gastric artery The main vascular supply of the hindgut derivatives is the
o Common hepatic artery  cystic artery inferior mesenteric artery, which further branches into:
o Gastroduodenal artery  superior pancreatic o Left colic artery
duodenal artery o Sigmoidal arteries
o Superior rectal arteries
Table 1. Vascular Supply and Mesentery of Foregut Derivatives
Foregut Vascular Supply Table 3. Vascular Supply and Mesentery of Hindgut Derivatives
Mesentery
Derivative Hindgut Vascular
Mesentery
Left gastric a. Greater omentum, Derivative Supply
Stomach
Lesser omentum Distal 1/3 of Left colic a.
Transverse
Spleen Left gastric a. Gastrosplenic ligament Transverse
mesocolon
Common hepatic a. Colon
Lesser omentum
o Hepatogastric Descending Left colic a. Retroperitoneal; no
Liver colon mesentery
o Hepatoduodenal
o Falciform Sigmoid Sigmoidal
Sigmoid mesocolon
Gallbladder Cystic a. Same as above colon arteries
Gastroduodenal a. Upper Superior rectal

Tail – splenorenal rectum artery
ligament (above the No mesentery
Pancreas Head & Body – pectinate
retroperitoneal; no line)
mesentery
Proximal half Gastroduodenal a. Hepatoduodenal
of duodenum ligament
2 of 3 EMBRYOLOGY: Note #13. Development & Embryology of the GI Tract P2

V) REVIEW QUESTIONS
1) The following is derived from the ventral

mesogastrium, EXCEPT?
a) Liver
b) Hepatogastric ligament
c) Hepatoduodenal ligament
d) Spleen
2) What is the mesentery/ligament supporting the
jejunum?
a) Hepatoduodenal ligament
b) Small bowel mesentery
c) Transverse mesocolon
d) It is not supported by a mesentery.
3) What vessel supplies the proximal transverse colon?
a) Ileo-colic artery
b) Right colic artery
c) Middle colic artery
d) Left colic artery
CHECK YOUR ANSWERS
VI) REFERENCE
Figure 4. Summary of Vascular Supply and Mesenteries
Development & Embryology of the GI Tract P2 EMBRYOLOGY: Note #1. 3 of 3

17. DEVELOPMENT OF FETAL CIRCULATION

Embryology | Development of Fetal Circulation Medical Editor: Sohani Kashi Puranic
OUTLINE Consequence
 As the whole pulmonary circuit undergoes
I) OVERVIEW
vasoconstriction,
II) BEFORE BIRTH
III) AFTER BIRTH
IV) PECULIARITIES OF FETAL CIRCULATION
V) CHANGES FROM FETUS TO ADULT o Because of this, Right side of heart (right
VI) ANOMALIES Atrium & ventricle) needs to generate high
VII) SUMMARY pressure to pump blood into the high-
VIII) APPENDIX pressure pulmonary circuit
IX) REVIEW QUESTIONS
X) REFERENCES
I) OVERVIEW
The circulation in fetuses is slightly different compared to Pressures in heart:
that seen in adults
Right side > Left side
Placenta is the organ responsible for gas exchange
Various remnants are present in adults, which represent
fetal structures of the fetal circulation
II) BEFORE BIRTH
(A) CONDITION OF LUNGS

In utero, that is before birth, the lungs are still developing
(B) HYPOXIC VASOCONSTRICTION

(1) Consequence of Hypoxia
Figure 1. Hypoxic Vasoconstriction
Due to hypoxia in the lungs, the pulmonary vasculature
undergoes vasoconstriction (C) STRUCTURES & PATHWAY
(1) Placenta
REMEMBER Plays a role in exchange of gases
The placenta is connected with the fetus through
Effect of Hypoxia on:
Umbilical cord
Systemic Vessels- Vasodilation Functions of Placenta
Pulmonary Vessels- Vasoconstriction Exchange of gases
 Occurs by simple diffusion
 O2 delivery to fetus is by placental blood flow
(2) Reason for Vasoconstriction in Hypoxia
Exchange of nutrients & electrolytes
The pulmonary capillaries near hypoxic alveoli undergo
vasoconstriction  Occurs rapidly
 Increases as pregnancy advances
Transmission of maternal antibodies

 IgG
By this, alveoli with more O2 concentration will receive  Provides PASSIVE I MMUNITY to fetus
better blood supply for effective ventilation
Hormone production
(3) Hypoxic Vasoconstriction in Fetus
 Progesterone
Condition in Fetus  Estriol
 hCG (human Chorionic Gonadotropin)
 Pulmonary circuit vasoconstriction normally occurs  Somatomammotropin/ hPL (human Placental
around hypoxic alveoli Lactogen)
 In Fetus- all alveoli have ↓O2 concentration
 This results in intense vasoconstriction throughout Protection
the pulmonary circulation  Protects fetus from damaging agents
 However, many drugs & viruses pass through
placenta easily
DEVELOPMENT OF FETAL CIRCULATION EMBRYOLOGY: Note #1. 1 of 8

(3) Umbilical Vein to IVC
Ductus Venosus
 It is a structure that shunts blood from (Left)
Umbilical Vein DIRECTLY into IVC
Sphincter Mechanism of Ductus Venosus

Regulates blood flow from Umbilical Vein
During uterine contraction:
Figure 2. Placenta
(2) Umbilical Cord
Components
Hepatic Sinusoids
(a) Blood Vessels  Umbilical vein also drains into the sinusoids of the
liver
(i) 2 Umbilical Arteries  These drain into the Hepatic portion of IVC
(ii) 1 Umbilical Vein (left)
 Carries Oxygenated blood
 85% O2 SATURATION (4) Right Atrium of Heart
(b) Wharton’s Jelly
o Mucopolysaccharide
 Rich in proteoglycans
 Provides insulation
 Protects the blood vessels
Figure 3. Structure of Umbilical Cord Figure 5. Openings in Right Atrium

(c) Remnant of vitelline duct Openings
(a) IVC (Inferior Vena Cava)
• Receives blood from:
(i) Ductus Venosus

(ii) Liver sinusoids
• Drains into Right Atrium
(b) SVC (Superior Vena Cava)

Figure 4. Umbilical Cord
• Receives blood from head, neck & upper
extremities
Termination of Umbilical Vein • Drains into Right Atrium
• Derived from Right Common Cardinal Vein
 Umbilical vein
ultimately pours its Pathways from Right Atrium
oxygenated blood
from placenta into  Blood from the right atrium can go to the following
IVC (Inferior Vena structures:
Cava)
(a) Left Atrium
 There are 2
pathways for the (b) Right Ventricle
blood from Umbilical
vein to IVC
Figure 4. Umbilical Vein &

Ductus Venosus
2 of 8 EMBRYOLOGY: Note #17. DEVELOPMENT OF FETAL CIRCULATION

(5) Left Atrium of Heart
70% of the blood from Right Atrium goes to Left Atrium
The connection between the Right & Left atria is
Foramen Ovale
Foramen Ovale
Figure 7. Formation of Umbilical Arteries

• This communication is called Foramen Ovale
Placenta
 Blood from Umbilical arteries drain into placenta,
where CO2 is given out
 O2 is taken up in the placenta, and oxygenated
blood is delivered to fetus via Umbilical vein
(8) Pathway from Right Ventricle

Blood to right ventricle:
i. Majority of Deoxygenated blood from SVC
ii. 30% of Oxygenated blood from IVC
Figure 6. Foramen Ovale
Blood from right ventricle is pumped into Pulmonary
(6) Right Ventricle of Heart
Trunk
The remaining 30% of blood from Right Atrium flows into From pulmonary trunk, it follows 2 pathways:
Right Ventricle
Ductus Arteriosus
Why majority of blood flows into Left Atrium  It is a structure that connects Pulmonary Artery
to Aorta
Blood flows from

High Pressure to Low Pressure
 It shunts the deoxygenated blood
Right side of heart: HIGH pressure

 Due to hypoxic vasoconstriction
Left side of heart: LOW pressure

 Relatively lower than right side
HENCE , MAJORITY OF B LOOD FROM

RIGHT ATRIUM (HIGH P RESSURE ) FLOWS INTO LEFT ATRIUM
(LOW PRESSURE ), Figure 8. Ductus Arteriosus
& NOT RIGHT VENTRICLE
Pulmonary Arteries
(7) Pathway from Left Atrium
 ↓↓↓ blood flows through Right & Left Pulmonary
Blood from right atrium passes through Foramen Ovale to arteries
reach the left atrium. From there, it goes to different  This blood reaches the developing lung
structures, in the following order: Why majority of blood flows through Ductus Arteriosus
Left Ventricle
Ascending Aorta, Arch of Aorta
Blood flows from
Descending Aorta
High Pressure to Low Pressure
Common Iliac Artery
Internal Iliac Artery
Umbilical Artery
Pulmonary Artery: HIGH pressure
 Carries Oxygenated blood mixed with
 Due to hypoxic vasoconstriction
Deoxygenated blood
 58% O2 SATURATION Aorta: LOW pressure
 Relatively lower pressure in left side of heart & aorta
HENCE , MAJORITY OF B LOOD FROM

PULMONARY ARTERY (HIGH PRESSURE ) FLOWS INTO AORTA
(LOW PRESSURE ),
& NOT THROUGH BOTH PULMONARY ARTERIES TO LUNG

,
Structures that shunt blood AWAY from

Pulmonary Circulation:
Foramen Ovale
Ductus Arteriosus
III) AFTER BIRTH
(A) EVENTS RIGHT AFTER BIRTH

(1) Umbilical Cord is cut
Connection between Placenta & Fetus is broken Figure 10. No hypoxic vasoconstriction
(B) CHANGES AFTER BIRTH

(1) Closure of Foramen Ovale
Pressure in left side of heart ↑
This is called the FUNCTIONAL closure of Foramen

Ovale
Figure 9. Umbilical Cord is cut after birth
(2) Lungs Anatomical closure occurs by fusion of Septum
secundum & Septum primum
Baby cries right after birth
 Allows for air to flush into lung
 O2 floods into alveoli
Consequence of no vasoconstriction
o Because of this, pressure on Right side of

heart (right Atrium & ventricle) ↓
OPPOSITE pressure gradient to that

seen before birth Figure 11. Fossa Ovalis
REMEMBER
Closure of Foramen Ovale:
Functional- Immediately after birth

Pressures in heart: Anatomical- 1 year after birth
Left side > Right side
Figure 12. Pulmonary Circulation

(2) Pulmonary Circulation Pathway for oxygenated blood:
There is now ↑ blood flow through the pulmonary circuit Pulmonary Veins
Pulmonary Arteries Left Atrium
 Carry deoxygenated blood from right ventricle to (2) Left Side of Heart
lungs
Left Atrium
Pulmonary Capillaries Left Ventricle
 Supply alveoli which are now well-ventilated Aorta
 Exchange of gases occurs at alveoli
(3) Systemic Circulation
Pulmonary Veins
Oxygenated blood is supplied to different organs via the
 Carry oxygenated blood from lungs to left atrium Aorta and its branches
(3) Closure of Ductus Arteriosus At the tissues,
 This means blood is deoxygenated

Pathway for deoxygenated blood:
Blood from lower extremities: Iliac Veins → IVC

Blood from head, neck, upper extremities: SVC
(4) Right Side of Heart
Figure 13. Closure of Ductus Arteriosus
IVC, SVC → Right Atrium
Ductus Arteriosus closes due to: Right Ventricle
O2 ↑ Pulmonary Trunk
PGE2 ↓
1
끫뢄2 ∝
끫뢆끫뢆끫뢆2 Ductus Arteriosus is closed. Before
closure, for a very short period,
Bradykinin ↑ blood is shunted to Aorta.
Hypoxia and ↑ PGE2 keep Ductus Arteriosus patent &
open before birth
(5) Pulmonary Circulation
After birth, the DA remains open for Pulmonary Trunk

a very short period of time before it Pulmonary Arteries
closes Pulmonary Capillaries
 Gas exchange occurs at alveoli, where the
deoxygenated blood is oxygenated
IV) PECULIARITIES OF FETAL CIRCULATION
(A) SHUNTING
Blood is shunted along its course at 3 points:
Ductus Venosus
 To direct blood to IVC by bypassing liver, without
losing O2 content
Figure 14. Factors affecting patency of DA
Foramen Ovale
(C) STRUCTURES & PATHWAY
 To equalize distribution to each half of heart, and
(1) Pulmonary Circulation more oxygenated blood to upper half vital organs
With air entering alveoli, and production of surfactant, the Ductus Arteriosus
lungs are now functional
Gas exchange occurs at alveoli where:  To direct blood to placenta for oxygenation by
bypassing lungs
[IB Singh]
 This means blood is oxygenated

(B) MIXING VI) ANOMALIES
During its course from placenta to the organs of the fetus,
blood in the Umbilical vein gradually loses its high oxygen (A) PATENT FORAMEN OVALE
content as it mixes with deoxygenated blood. [Langman] Foramen Ovale doesn’t close
Places where mixing occurs:
Table 1. Sites of mixing of Oxygenated & Deoxygenated Blood
Oxygenated Deoxygenated
Site
Blood Blood
Liver Umbilical
Portal system
vein
IVC Umbilical Lower

vein extremities
Right Umbilical
+ Upper
Atrium vein blood
extremities
from IVC
From Right
Left Atrium
Atrium through From Lungs
Foramen
Ovale Figure 15. Patent Foramen Ovale
[mayoclinic.org]
Ductus Pulmonary
Aorta
Arteriosus Trunk (B) PATENT DUCTUS ARTERIOSUS
Ductus Arteriosus doesn’t close
(C) NICE TO KNOW
IVC carries the most oxygenated blood in fetus
More oxygenated blood is delivered to Upper Limbs
Upper limbs > Lower Limbs
V) CHANGES FROM FETUS TO ADULT

Table 2. Postnatal occlusion of vessels/ structures & their
remnants
Structure Remnant
Left Umbilical Vein Ligamentum Teres Hepatis
Umbilical Arteries
i. Proximal part i. Superior Vesical
Artery
ii. Distal part ii. Medial Umbilical
Ligament
Ductus Venosus Ligamentum Venosum
Ductus Arteriosus Ligamentum Arteriosum
Foramen Ovale Fossa Ovalis
REMEMBER
Remnant of:
Figure 16. Patent Ductus Arteriosus
UmbilicAL Arteries- MediAL Umbilical Ligaments [Netter’s Atlas]
Allantois (Urachus)- Median Umbilical Ligament
(C) PORTAL HYPERTENSION
Ligamentum teres hepatis recanalizes

VII) SUMMARY
Figure 17. Development of Fetal Circulation
VIII) APPENDIX
Figure 18. Fetal Circulation & Transition to Post-natal Circulation

[Netter’s Atlas]

IX) REVIEW QUESTIONS X) REFERENCES
1) Which is NOT essential for maintenance of fetal Cochard, L. R., & Netter, F. H. (2002). Netter's atlas of human
circulation? embryology. Teterboro, N.J: Icon Learning Systems.
Inderbir Singh, Pal GP. Human Embryology. 8th ed. India: Mac
a) Foramen ovale
Millan Publishers Limited; 2007.
b) Ductus arteriosus Sadler TW. Langman's Medical Embryology. Philadelphia:
c) Renal veins Wolters Kluwer; 2019.
d) Inferior Vena Cava Le T. First Aid for the USMLE Step 1 2020. 30th anniversary
edition: McGraw Hill; 2020.
Marieb EN, Hoehn K. Anatomy & Physiology. Hoboken, NJ:
Pearson; 2020.
2) Which structure carries the most oxygenated blood Boron WF, Boulpaep EL. Medical Physiology.; 2017.
in fetus?
a) Umbilical vein
b) Renal vein
c) Inferior vena cava
d) Umbilical artery
3) What is the remnant of umbilical arteries?

a) Ligamentum arteriosum
b) Superior vesical artery
c) Ligamentum teres hepatis
d) Ligamentum venosum
4) What is the concentration of oxygen in Umbilical

Artery?
a) 15%
b) 28%
c) 58%
d) 85%
5) Ductus arteriosus connects pulmonary artery to

which of the following?
a) Pulmonary vein
b) Foramen ovale
c) Subclavian artery
d) Aorta
6) Before birth, blood is shunted:

a) Away from pulmonary circulation
b) Towards pulmonary circulation
c) No shunts present
d) Both a & b, according to respiration
7) What is the remnant of urachus?

a) Medial umbilical ligament
b) Lateral umbilical ligament
c) Median umbilical ligament
d) Ligamentum teres
8) Ductus arteriosus is sensitive to all EXCEPT:

a) Prostaglandins
b) Leukotrienes
c) Oxygen
d) Bradykinin
CHECK YOUR ANSWERS

1. DEVELOPMENT OF THE MUSCULAR SYSTEM

Development of the Muscular System Medical Editor: Jan Camille Santico
OUTLINE II) INFERIOR HYOID, TRUNK, AND GIRDLES
I) HEAD AND NECK Recall: The paraxial mesoderm undergoes segmentation

II) INFERIOR HYOID, TRUNK, AND GIRDLES to form somites flanking the neural tube
III) LIMBS o Three somites are formed each day until there are 44-
IV) MUSCLE FORMATION 45 somites by the 5th week of development
V) REVIEW QUESTIONS o A cavity within the somites (somitocele) forms
VI) REFRENCES
The somitocele continues to expand, dividing into a
Note: It is recommended that you watch the video on the
dorsal and ventral portion
“Development of the Skeletal System” before this.
o Dorsal: dermatomyotome
I) HEAD AND NECK  Dermatome – forms the dermis
 Myotome – forms muscle
Visualize a sagittal section through the primitive pharynx o Ventral: sclerotome – forms bones and cartilage
Along the cranial end of the embryo is the o Syndetome – a layer between the myotome and
buccopharyngeal membrane sclerotome which develops into tendons
o Fusing of the ectoderm and endoderm layers
(A) TRUNK
The pharynx forms vesiculations, forming the pharyngeal
apparatus, which has three layers: The sclerotome wraps around the neural tube to form the
o Outer layer: Ectoderm bony casing of the spinal cord and thoracic cage:
o Core: Mesoderm o Vertebrae
o Inner layer: Endoderm o Intervertebral discs
o Ribs
The mesoderm within the 1st – 4th and 6th arches undergo
a differentiation process to form the muscles of the head The myotome is further split into:
and suprahyoid muscles o Dorsal/Medial
The muscles each have their own innervation  Forms the muscles of the back
 Epiaxial muscles
o Ventral/Lateral
 Forms the muscles of the trunk and limbs
 Hypaxial muscles
Figure 1. Development of the Pharyngeal Arches

Table 1. Muscles derived from the Pharyngeal Arches
Pharyngeal Nerve Supply
Muscle Derivatives
Arch
Muscles of mastication CN V
o Temporalis (Trigeminal
o Masseter nerve)
1st o Pterygoids
Mylohyoid
Digastric (anterior belly)
Tensor veli palatini
Muscles of facial expression CN VII
Stylohyoid (Facial nerve)
2nd Figure 2. Development of the Somites
Digastric (posterior belly)
Stapedius
CN IX
3rd Stylopharyngeus (Glossopharyngeal
nerve)
Levator veli palatini CN X
th th Pharyngeal constrictor (Vagus nerve)
4 and 6
muscles
Laryngeal muscles
Development of the Muscular System EMBRYOLOGY: Note #1. 1 of 3

(B) EPIAXIAL MUSCLES III) LIMBS
These muscles are derived from the dorsal/medial portion
Recall: The limbs are initially start as ectodermal
of the myotome
outpouchings called limb buds
The epiaxial muscles surround the base of the skull and
o The following genes induce limb bud formation and
the vertebrae, all the way down to the pelvic girdle
dictate their position:
The back muscles include:
 Hox
o Erector spinae
 TBx4
o Multifidi muscles
 TBx5
o Semispinalis capitis
 FGF 10
o Suboccipital muscles
The somatic mesoderm (from lateral plate mesoderm)
(C) HYPAXIAL MUSCLES migrate to the limb buds to form the limb skeleton
These muscles are derived from the ventral/lateral portion o The apical ectodermal ridge (AER) drives the
of the myotome proximal to distal formation of the limb skeleton
The hypaxial muscles form the: The syndetome migrates to the limb buds to form the
o Trunk muscles tendons
 Diaphragm The myotome migrates to the limb buds to form the
 Intercostal muscles muscles
 Serratus anterior and posterior o Initially, the myotome forms nonspecific chunks of
 Abdominal muscles muscle
o Limbs o Eventually, the chunks differentiate based on their
 Upper limb muscles anatomical position (anterior, posterior)
 Lower limb muscles o The embryological structures lead to functional
o Infrahyoid muscles/ “strap” muscles differences (See Table 2)
 Scalene  For example, the anterior condensation forms the
flexor and pronator muscles of the upper limbs
The dermatome migrates to the limb buds to form the
dermis and subcutaneous tissue
Table 2. Muscles of the Limbs

Condensation Upper Limbs Lower Limbs
Extensors
Anterior Flexors Dorsiflexors
Pronators Adductors
Flexors
Posterior Extensors Plantar flexors
Supinators Abductors
Figure 3. Development of the Epiaxial and Hypaxial

Muscles
Figure 4. Development of the Limb Muscles
2 of 3 EMBRYOLOGY: Note #1. Development of the Muscular System

IV) MUSCLE FORMATION V) REVIEW QUESTIONS
Muscles generally come from the mesoderm 1) The muscles of facial expression develop from which
The epithelial mesoderm cells transition into pharyngeal arch?
mesenchymal cells a) 1st
The mesenchymal cells transform to myoblasts b) 2nd
c) 3rd
d) 4th
These muscle cells need genes to differentiate: 2) The following structures are derived from the 4th
o The first gene to be activated is the Pax gene pharyngeal arch EXCEPT:
o Pax gene is activated a) Stylopharyngeus
b) Pharyngeal constrictor muscles
c) Laryngeal muscles
These genes are necessary for the production of proteins d) Levator veli palatini
which make muscle cells phenotypically different 3) Which of the following muscles is derived from the
dorsal/medial portion of the myotome?
a) Semispinalis capitis
b) Serratus anterior
c) Scalene
d) Transversus abdominus
4) Which of the following statements is FALSE?
a) The anterior condensation gives rise to the flexor
muscles of the upper limbs
b) The anterior condensation gives rise to the
dorsiflexors of the lower limbs
c) The posterior condensation gives rise to the
adductor muscles of the lower limbs
d) The posterior condensation gives rise to the
Figure 5. Muscle Formation
supinator muscles of the upper limbs
5) Which gene is crucial for the production of muscle-
specific proteins?
a) Hox
b) Sox9
c) TBx4
d) Pax
CHECK YOUR ANSWERS
VI) REFRENCES
Development of the Muscular System EMBRYOLOGY: Note #1. 3 of 3

1. DEVELOPMENT OF PHARYNGEAL APPARATUS

Embryology: Development of Pharyngeal Apparatus Medical Editor: Dr. Sofia Suhada M. Uzir
OUTLINE (iv) Pharyngeal pouches

o Made out of endoderm
I) INTRODUCTION
o There are 4 pharyngeal pouches
II) PHARYNGEAL CLEFTS/GROOVE
o The 3rd and 4th will split into
III) PHARYNGEAL ARCHES
IV) PHARYNGEAL POUCHES  Dorsal pouch
V) REVIEW QUESTIONS  Ventral pouch Figure 4
VI) REFERENCES o Will develop into
 Epithelium
• Lining cavities
 Glands
I) INTRODUCTION • Parathyroid
• Thymus
(1) Location
Located at the cranial end of a sagittal section of an II) PHARYNGEAL CLEFTS/GROOVE
embryo
At the outer parts and covered with ectoderm
Gill like structure
Will become the epithelium
o The 1st cleft develops into tissue lining the external
ear canal
III) PHARYNGEAL ARCHES

Mesoderm core (mesenchymal tissue)
(A) MUSCLE
st
(1) 1 arch
Muscle of mastication supplied by trigeminal nerve
o Medial and lateral pterygoids
o Masseter
o Temporalis
Mylohyoid / anterior belly of digastric
o Suprahyoid muscles
Tensor veli palatini
o Movement of soft palate during swallowing
Figure 1. Parts of pharyngeal apparatus
(2) 2nd arch
(2) Parts in pharyngeal apparatus Figure 1 Muscles of facial expression
Pharyngeal apparatus consists of Stylohyoid / posterior belly of digastric muscle
o Suprahyoid muscles
(i) Buccopharyngeal membrane Stapedius
o Connects endoderm and ectoderm layer o In the middle ear
o Becomes the mouth o Helps in control in sensitivity of hearing
(ii) Pharyngeal clefts/groove (3) 3rd arch
o At the outer parts and covered with ectoderm Stylopharyngeus supplied by glossopharyngeal nerve
o Will become the epithelium o For deglutition
 The first cleft develops into tissue lining the (4) 4th and 6th arches
external ear canal
Pharyngeal constrictor muscles
(iii) Pharyngeal arches o Superior, middle and inferior constrictors
o There are 6 arches o Helps in deglutition
o The 5th usually doesn’t form/digress Laryngeal muscles
o Mesoderm core (mesenchymal tissue) o Cricothyroid
o Will develop into o Arytenoid
 Muscle
Levator veli palatini
 Connective tissue
o Helps in deglutition
 Cartilage
• Laryngeal
 Bone
 Nerves
DEVELOPMENT OF PHARYNGEAL APPARATUS EMBRYOLOGY: Note #1. 1 of 3

(B) BONE AND CONNECTIVE TISSUES (C) NERVES
Figure 3. Nerves of pharyngeal arches

Figure 2. Bones and ligaments developed (1) 1st arch
(1) 1st arch Trigeminal nerve
Almost the entire skull Figure 2 o Cranial nerve 5
o Maxilla (2) 2nd arch
o Zygomatic bones
o Mandible Facial nerve
o Squamous part of temporal bone with its processes o Cranial nerve 7
 Styloid process (3) 3rd arch
 Mastoid process
 Zygomatic process Glossopharyngeal nerve
o Malleus and Incus o Cranial nerve 9
 Bones in the middle ear
(4) 4th and 6th arch
(2) 2nd Vagus nerve
Hyoid bone o Cranial nerve 10
o Some of it comes from the 3rd arch  Superior laryngeal nerve (4th arch)
 Recurrent laryngeal nerve (5th arch)
Stylohyoid ligament
o Connecting hyoid bone to styloid process (D) ARTERIES
Stapes (1) 1st arch
o Bones in the middle ear
o Taps on the oval window Maxillary artery
(3) 4th and 6th arch (2) 2nd arch
Laryngeal cartilages Hyoid artery → stapedial artery

o Thyroid cartilage Only 10% remains in adulthood
o Arytenoid cartilage (3) 3rd arch
o Cuneiform/corniculate
Common carotid artery
Proximal portion of internal carotid artery
(4) 4th arch
Right
o Subclavian artery
Left
o Aortic arch
(5) 6th arch
Right
o Right pulmonary artery
Left
o Left pulmonary artery
o Ductus arteriosus
 Connects pulmonary trunk to aorta
2 of 3 EMBRYOLOGY: Note #1. DEVELOPMENT OF PHARYNGEAL APPARATUS

IV) PHARYNGEAL POUCHES V) REVIEW QUESTIONS
Made out of endoderm Parafollicular cells of thyroid gland are derived from
which endodermal pouch?
a. 1st and 2nd
b. 2nd and 3rd
c. 3rd and 4th
d. 4th and 5th
Which of the muscles attaching to the styloid
process is NOT derived from a pharyngeal arch?
a. Styloglossus
b. Stylopharyngeus
c. Stylohyoid
d. Levator veli palatine
e. Tensorteli palatini concerning
Figure 4. Pharyngeal pouches The nerve delivering sensory innervation to the
posterior side of the external ear canal is a
(A) EPITHELIUM pretrematic nerve supplying derivatives branch of
the cranial of the fourth pharyngeal arch. It is the:
(1) 1st pouch a. Greater petrosal nerve
Endoderm moves into the middle ear cavity b. Nerve of the pterygoid canal
o Tympanic cavity c. Auricular nerve (of Arnold)
o Eustachian tube d. Tympanic nerve (of Jacobson)
 Drains Into nasal cavity e. Deep petrosal nerve
The muscular derivatives of the 2nd pharyngeal arch
(2) 2nd pouch are all except?
Lymphatic tissue/tonsils a. platysma
o Specifically pharyngeal tonsil b. stylohyoid
 At the back of nasopharynx c. mylohyoid
o Others: d. posterior belly of digastric
 Palatine, tubal, lingual tonsils e. muscles of facial expression
the bone derivatives of the 1st arch include all of the
Lines the naso-oral cavity following except?
(3) 3rd pouch a. Maxilla
b. Zygomatic bones
Dorsal c. Mandible
o Inferior parathyroid glands d. Stapes
 Located at the back and bottom part of thyroid The epithelium derivative of the 1st pouch lines the:
o During development, the 4th dorsal pouch moves a. Tympanic cavity
upwards hence gives the superior parathyroid b. Inferior parathyroid glands
gland c. naso-oral cavity
Ventral d. Superior parathyroid glands
o Thymus The epithelium derivative of the 2nd pouch lines the:
o Lymphatic tissue a. Eustachian tube
o Starts in the neck then moves down to the chest b. Naso-oral cavity
where T-cells mature c. Tympanic cavity
d. Superior parathyroid glands
(4) 4th pouch The muscle derivatives of the 2nd arch include:
Dorsal a. Stylopharyngeus
o Superior parathyroid glands b. Stapedius
c. Cricothyroid
Ventral
d. Arytenoid
o Ultimopharyngeal body → parafollicular cells (C-cells)
the bone derivatives of the 3rd arch include:
 Secrete calcitonin which helps regulate calcium
a. Hyoid bone
(B) CLINICAL SIGNIFICANCE b. Thyroid cartilage
c. Zygomatic bones
DiGeorge syndrome
d. Mandible
o 3rd and 4th pouches malformation
In DiGeorge syndrome
o Absent or poorly developed thymus and parathyroid
a. Immunity is normal
glands
b. Calcium metabolism increases
 Immunity issues due to impaired T-cell
c. There is malformation of 3rd and 4th pharyngeal
development
pouches
o Parafollicular cells which secrete calcitonin
d. The thymus is unaffected
 Calcium metabolism will be affected
CHECK YOUR ANSWERS
VI) REFERENCES
Sadler TW. Langman's Medical Embryology. Philadelphia:
Wolters Kluwer; 2019.
Le T. First Aid for the USMLE Step 1 2020. 30th anniversary
Marieb EN, Hoehn K. Anatomy & Physiology. Hoboken, NJ:
Pearson; 2020.
Boron WF, Boulpaep EL. Medical Physiology.; 2017.
DEVELOPMENT OF PHARYNGEAL APPARATUS EMBRYOLOGY: Note #1. 3 of 3

16. DEVELOPMENT OF THE REPRODUCTIVE TRACT

Development of the Reproductive Tract Medical Editor: Jan Camille Santico
OUTLINE II) GONADS AND DUCTAL SYSTEMS
I) PRIMITIVE REPRODUCTIVE TRACT Each fetus has two bipotential gonads and a ductal
II) GONADS AND DUCTAL SYSTEMS system which empties into the urogenital sinus
III) EXTERNAL GENITALIA The ductal system is made up of the following:
IV) APPENDIX o Mesonephric / Wolffian Ducts
V) REVIEW QUESTIONS o Paramesonephric / Mullerian Ducts
VI) REFERENCES o Gubernaculum
During sexual differentiation, the changes occur in
different parts of the gonadal structure
o In males, changes occur in the medulla
o In females, changes occur in the cortex
I) PRIMITIVE REPRODUCTIVE TRACT
Recall:
The reproductive system develops from the mesoderm, o Males have the XY chromosome
which has three types: o Females have the XX chromosome
o Paraxial
o Intermediate
o Lateral plate
 Somatic layer (closer to the ectoderm)
 Splanchnic layer (closer to the endoderm)
The reproductive tract is derived from the intermediate
mesoderm
The intermediate mesoderm will condense and form the
urogenital ridge, which will give rise to the:
o Gonads
o Ductal system
From the sagittal section of the embryo, the gut tube can
be visualized
o The hindgut area contains the cloaca, which gives
rise to two canals separated by the urorectal septum:
 Urogenital sinus (anterior) Figure 2. Development of the Reproductive Tract
 Anal canal (posterior)
(A) MALES
The yolk sac contains the primordial germ cells (PGCs),
which will: The Y chromosome contains the SRY gene
o Migrate through the vitelline duct; and
o Invade the urogenital ridge
The PGCs will give rise to the gametes (sperm and The testes are made up of:
oocytes) o Seminiferous tubules
o Rete testes
o Leydig cells – produce testosterone
o Sertoli cells – produce Mullerian-inhibiting
Factor/Hormone
o Sperm – arise from the PGCs
Testosterone from the Leydig cells:
o Stimulates the growth of the mesonephric/Wolffian
duct, which gives rise to the:
 Epididymis
 Vas deferens
 Seminal vesicles
 Common ejaculatory duct
o Is converted to Dihydrotestosterone (DHT) via the
enzyme 5-alpha reductase
 DHT stimulates the formation of the male external
genitalia
Mullerian-inhibiting factor from the Sertoli cells inhibit the
growth of the paramesonephric/Mullerian ducts
The gubernaculum guides the descent of the testes into
the scrotum
o Pulls down the ductal system and the testes to the
scrotum, forming the spermatic cord
Figure 1.Development of the Urogenital Ridge
Development of The REproductive Tract EMBRYOLOGY: Note #1. 1 of 4

(B) FEMALES III) EXTERNAL GENITALIA
In females, there is no Y chromosome
The primitive external genitalia are made up of:
o Genital tubercle
o Labioscrotal swellings
In the absence of TDF, the gonads differentiate into o Urethral folds
ovaries by default o Urogenital sinus
The ovaries are made up of:
From the sagittal view, one can visualize the cloaca as it
o Follicular cells – produce estrogen
splits into:
o Oocytes – arise from PGCs
o Urogenital sinus
The estrogen from follicular cells will stimulate the o Anal canal
formation of the female external genitalia
The mesonephric duct will empty into the urogenital sinus
Since there is no testosterone, the mesonephric/Wolffian
ducts will regress/not develop
Since there is no Mullerian-inhibiting hormone, the
paramesonephric/Mullerian ducts will grow, giving rise to:
o Fallopian tube
o Uterus
o Upper 2/3 of vagina
The gubernaculum guides the descent of the ovaries and
ductal system into the pelvis
o It eventually splits to form:
 Ovarian ligament – connects the ovary and
uterus Figure 4. Development of the External Genitalia
 Round ligament – connects the uterus and labia
(A) MALES
DHT stimulates the formation of the external genitalia in
males
The primitive structures and their derivatives include:
o Genital tubercle
 glans penis
 corpus spongiosum
 corpus cavernosum
o Labioscrotal Swelling – scrotum
o Urogenital sinus
 prostatic urethra
 membranous urethra
 prostate gland
Figure 3. Differentiation of the Male and Female  Cowper’s/bulbourethral gland
Reproductive Tracts o Urethral folds
 shaft of penis
(C) UROGENITAL SINUS  penile urethra
The ducts empty into the urogenital sinus
(B) FEMALES
The urogenital sinus gives rise to the:
o Bladder Estrogen stimulates the formation of the external
o Part of the urethra (prostatic urethra) genitalia in females
The primitive structures and their derivatives include:
o Genital tubercle
 clitoris
 vestibular bulbs
o Labioscrotal Swelling – labia majora
o Urogenital sinus
 bladder
 female urethra
 paraurethral glands
 Bartholin’s glands
o Urethral folds – labia minora
Figure 5. Differentiation of the Male and Female External

Genitalia
2 of 4 EMBRYOLOGY: Note #16. Development of The REproductive Tract

IV) APPENDIX
Table 1-1 Summary of Primitive Reproductive Tract Structures and Their Derivatives
Structure Males Females
Primordial Germ Cells Sperm Oocytes
Gonads Testes Ovaries
Epididymis None (regresses)
Mesonephric / Wolffian Ducts Vas deferens
Common ejaculatory duct
Uterus
Paramesonephric / Mullerian Ducts None (regresses) Fallopian tubes
Upper 2/3 of vagina
Ovarian ligament
Gubernaculum Spermatic cord
Round ligament
Bladder Bladder
Prostatic urethra Female urethra
Urogenital Sinus Membranous urethra Paraurethral glands
Prostate gland Bartholin’s glands
Cowper’s / Bulbourethral gland
Glans penis Clitoris
Genital Tubercle Corpus spongiosum Vestibular bulbs
Corpus cavernosum
Labioscrotal Swellings Scrotum Labia majora
Shaft of penis Labia minora
Urethral Folds
Penile urethra
6) The genital tubercle becomes what structure/s in

V) REVIEW QUESTIONS
females?
1) Which is responsible for the differentiation of the a) Clitoris
bipotential gonad into a testis? b) Vestibular bulbs
a) TDF c) Both A and B
b) Mullerian-inhibiting Factor d) Neither A nor B
c) Testosterone
d) DHT 7) The shaft of the penis develops from which primitive
structure?
2) Which is responsible for the differentiation of the a) Urethral Folds
external female genitalia? b) Labioscrotal Swellings
a) SRY c) Genital Tubercle
b) Progesterone d) Urogenital sinus
c) Estrogen
d) Luteinizing Hormone 8) The following are structures of the male reproductive
tract, EXCEPT
3) Which of the following was NOT derived from the a) Seminiferous tubules
urogenital sinus? b) Paraurethral glands
a) Bladder c) Cowper’s glands
b) Membranous urethra d) Sertoli cells
c) Penile urethra
d) Prostatic urethra 9) The gubernaculum develops into which structure in
the female reproductive tract?
4) In the absence of the SRY gene, which of the a) Labia minora
following occurs? b) Fallopian tube
a) The Mullerian duct regresses c) Round ligament
b) The cloaca splits into the urogenital sinus and anal d) Bartholin’s glands
canal
c) The gubernaculum guides the descent of the testes 10) Which of the following secretes the Mullerian-
into the scrotum inhibiting factor?
d) The gonads will differentiate into ovaries a) Prostate gland
b) Cowper’s gland
5) The Mullerian duct becomes what structure/s in c) Sertoli cells
males? d) Leydig cells
a) Epididymis
CHECK YOUR ANSWERS
b) Vas deferens
c) Both A and B
VI) REFERENCES
d) Neither A nor B
Development of The REproductive Tract EMBRYOLOGY: Note #1. 3 of 4

4 of 4 EMBRYOLOGY: Note #16. Development of The REproductive Tract
1. DEVELOPMENT OF THE SKELETAL SYSTEM

Development of the Skeletal System Medical Editor: Jan Camille Santico
OUTLINE
I) SKULL
II) TRUNK
III) LIMBS
IV) INTRAMEMBRANOUS VS ENDOCHONDRAL
V) REVIEW QUESTIONS
VI) REFRENCES
I) SKULL
In the development of the skeletal system, there are two
primary goals:
o Form the axial skeleton (skull, thoracic cage)
o Form the appendicular skeleton (limbs)
The skull develops from mesoderm and neural crest
cells
(A) NEUROCRANIUM
The neurocranium is the part of the skull which
encases/surrounds the brain
Recall: Trilaminar disc
o Superior to the neural tube are neural crest cells
o Flanking the neural tube are somites, which develop
from the segmentation of the paraxial mesoderm
The occipital somites (located towards the cranial end Figure 1. Development of the Chondrocranium
of the embryo) and the neural crest cells migrate
cranially to from the neurocranium (2) Membranous Neurocranium
The neurocranium can be divided into three regions: The membranous neurocranium is developed through
o Posterior cranial fossa intramembranous ossification
o Middle cranial fossa o The mesenchymal cells convert directly to bone tissue
o Anterior cranial fossa
The bones forming the membranous neurocranium
The neurocranium can be divided into two types based on include:
the process of bone formation: o Frontal bone
o Chondrocranium o Parietal bone
o Membranous neurocranium o Occipital bone
 The top part is formed through intramembranous
(1) Chondrocranium / “Base of the Skull”
ossification, while the bottom part is formed
This part of the neurocranium is developed through through endochondral ossification
endochondral ossification
o Most bones are developed through this process
o The mesenchymal cells (of the paraxial mesoderm)
differentiate into chondrocytes first before
differentiating into osteoblasts
o Mesenchymal cell  chondrocytes  osteoblasts
The base of the skull is made up of the following bones:
o Occipital bone
o Petrous part of temporal bone
o Sphenoid bone
o Ethmoid bone
Figure 2. Development of the Membranous Neurocranium
Development of the Skeletal System EMBRYOLOGY: Note #1. 1 of 5

(3) Sutures (4) Fontanelles
Sutures are fibrous joints connecting the bones of the Fontanelles are open areas of the skull where two bones
skull come together
The cranial sutures include: These give allowance for brain growth/expansion
o Coronal suture – connects the frontal bone and two There are two fontanelles:
parietal bones o Anterior
o Sagittal suture – connects the two parietal bones o Posterior
o Lambdoid suture – connects the two parietal bones to The posterior fontanelle closes first before the anterior
the occipital bone The fontanelles will bulge out if cerebrospinal fluid (CSF)
When the sutures close too early during the development is elevated
of a fetus/infant, it can cause craniosynostosis
(B) VISCEROCRANIUM
The viscerocranium forms the bones of the face
It develops from the pharyngeal arches, particularly the
first
The pharyngeal arches are made up of three layers:
o Outer layer – ectoderm
o Middle core – mesoderm (develops into
viscerocranium)
o Inner layer – endoderm (develops into the primitive
pharynx)
Figure 4. Viscerocranium (Intramembranous)
(2) Bones formed through Endochondral Ossification

In endochondral ossification: mesenchymal cell 
chondrocytes  osteoblasts
The parts of the viscerocranium which undergo this
Figure 3. Pharyngeal Arches process are:
o Hyoid bone
(1) Bones formed through Intramembranous o Laryngeal cartilages (thyroid, cricoid, arytenoid)
Ossification o Bones in the middle ear (malleus, incus)
In intramembranous ossification: mesenchymal cell  o Stapes (from the 2nd pharyngeal arch)
osteoblasts
The parts of the viscerocranium which undergo this
process are:
o Mandible
o Maxilla
o Zygomatic bones
o Temporal bone
 Squamous part of temporal bone
 External acoustic meatus
Figure 5. Viscerocranium (Endochondral)
2 of 5 EMBRYOLOGY: Note #1. Development of the Skeletal System

II) TRUNK
(A) VERTEBRA AND RIBS
(B) STERNUM
• Recall: The paraxial mesoderm segments to form
somites Recall: The lateral plate mesoderm is divided into a
o The somites develop a cavity called a somitocoele, splanchnic and somatic layer
which expands and divides the somites into dorsal The lateral plate mesoderm located on the anterior
and ventral parts portion of the embryo undergoes endochondral
 Dorsal – dermatomyotome ossification
 Ventral – sclerotome o Mesenchymal cells  chondrocytes  osteoblasts
o The dermatomyotome forms the dermatome and The formed bone tissue will fuse and form the three
myotome components of the sternum:
o The sclerotome develops into the bones of the o Manubrium (fused to the body via the sternal angle of
vertebrae and ribs Louie)
Recall: Spinal nerves need to exit the spinal cord to o Body
innervate target structures; however, there is no “hole” to o Xiphoid process
pass through The ribs will extend and connect to the sternum
o Somites undergo re-segmentation to form
intervertebral spaces along the vertebral body for
the spinal nerves to pass through
o In re-segmentation, the rostral segments fuse with the
caudal segment of the somite above
The sclerotome surrounds the neural tube to form the
vertebra
o Dorsally, they form the vertebral arches and fuse to
form the spinal process
o Ventrally or anteriorly, they form the vertebral bodies
and the intervertebral discs
o Laterally, they form the transverse process
 Bone will continue to form from this process,
forming the ribs
Figure 6. Development of the Trunk

III) LIMBS
(A) LIMB BUDS

The position of the limb buds is dictated by the following
genes:
o Hox genes
o TBx4
o TBx5
The TBx genes will dictate the position of the upper and
lower limbs
o When these genes are activated, they help with the
production of growth factors (FGF-10), which
stimulate the growth of limb buds
Initially, the limb buds are an outpouching of the
ectoderm. Eventually, the somatic layer of the lateral
plate mesoderm will move into the limb buds.
FGF-10 stimulates the growth of the limb buds and
stimulates the tips of the limb buds to form a thickened
area called the apical ectodermal ridge (AER)
(B) APICAL ECTODERMAL RIDGE

The AER will secrete growth factors (e.g. FGF-4, FGF-8)
which stimulates the invading mesoderm to proliferate
The AER and its secreted growth factors are responsible
for the proximal to distal growth of the limb skeleton
o The mesoderm closest to the AER is referred to as
the progress zone (PZ)
 A zone which focuses on proliferation instead of
differentiation
o Meanwhile, the mesoderm far from the AER focuses
on differentiation instead of proliferation
 Growth factors are not saturated in this area
 The mesoderm here differentiates into cartilage
and bone
 The most proximal area forms the stylopod,
which differentiates into the humerus
As the progress zone keeps extending/moving distally,
the relatively proximal areas left behind differentiate into
Figure 7. Development of the Limb Buds
cartilage and bone
o This forms the zeugopod, which differentiates into (C) DORSAL-VENTRAL DIFFERENTIATION
the forearm
Within the hand, the dorsal portion has condensing tissue
o The autopod differentiates into:
called the zone of polarizing activity (ZPA), which
 Carpal bones
drives the anterior and posterior development of the
 Metacarpals
thumb
 Phalanges
The ZPA releases molecules which create a gradient that
Some tissue in the AER will undergo apoptosis due to stimulates the differences in our fingers
bone morphogenetic protein (BMP) and retinoic acid Dorsal Growth
o The apoptosis of these tissues leads to the formation o Wnt 7A genes  LMX1  development of the dorsal
of fingers side + growth of nails
o AER still releases FGF, which stimulates the progress
Ventral Growth
zone to proliferate/extend the fingers/digits
o Engrailed-1  development of the ventral side +
Eventually, the AER will start dying and the FGF levels formation of finger prints
will drop
The dorsal and ventral aspect of the hands are dictated
o As a result, the progress zone will stop proliferating
by the ectoderm
and just differentiate
In summary, the AER drives the activity of the progress
zone
Figure 8. Dorsal-Ventral Differentiation
4 of 5 EMBRYOLOGY: Note #1. Development of the Skeletal System

IV) INTRAMEMBRANOUS VS ENDOCHONDRAL V) REVIEW QUESTIONS
These two processes of bone formation are also based 1) Which two structures are important for the
on gene expression development of the skull?
Intramembranous Ossification a) Occipital somites and neural crest cells
o Mesenchymal cells have genes which stimulate the b) Occipital somites and AER
formation of bone tissue c) Cervical somites and neural crest cells
o The expression of the CBFA and RUNX2 genes lead d) Cervical somites and AER
to the production of osteoids and other proteins which 2) Which of the following was NOT developed through
are responsible for the phenotypic development of endochondral ossification?
osteoblasts a) Sphenoid bone
Endochondral Ossification b) Ethmoid bone
o The Sox9 gene is responsible for the conversion of c) Parietal bone
mesenchymal cells to chondrocytes d) Occipital bone
3) The first pharyngeal arch differentiates into which of
the following structures?
a) Frontal bone
b) Zygomatic bone
c) Stapes
d) Clavicle
4) Which part of the somite will differentiate into the
vertebral bodies?
a) Dermatome
b) Myotome
c) Sclerotome
d) All of the above
5) The ribs arise form which structure?
Figure 9. Types of Ossification a) Dermatome
b) Myotome
c) Sclerotome
d) All of the above
6) All of these genes dictate the position of the limb
buds, EXCEPT?
a) Wnt4
b) TBx4
c) TBx5
d) Hox
7) The apical ectodermal ridge produces ____ to
stimulate the growth of the limb buds.
a) Osteoid
b) FGF
c) VEGF
d) Collagen
8) Which of the two pairs is correctly matched?
a) Stylopod: Hand
b) Autopod: Humerus
c) Zeugopod: Forearm
d) Stylopod: Fingers
9) The dorsal and ventral differentiation of the hand is
carried out by which germ derivative?
a) Ectoderm
b) Mesoderm
c) Endoderm
d) None of the above
10) All of the following are formed through
intramembranous ossification except?
a) Parietal bone
b) Mandible
c) Hyoid bone
d) Clavicle
CHECK YOUR ANSWERS
VI) REFRENCES

1. DEVELOPMENT OF THE HEART

Embryology | Development of the Heart Medical Editor: Uta Hüning
OUTLINE (1) VEGF

Endoderm secrets VEGF (vascular endothelial GF)
I) RECAP GASTRULATION VEGF stimulates mesoderm to differentiate:
II) HEART TUBE
o Angioblasts → heart tube, blood vessels
III) CARDIAC LOOPING
o Hemocytoblasts → blood cells
IV) SEPTA AND A-V VALVES
V) HEART CHAMBERS Lateral mesoderm grows, forms cavities
VI) INFLOW AND OUTFLOW TRACKS o Heart tubes
VII) SEMILUNAR VALVES o Pericardial cavities
VIII) APPENDIX
I) RECAP GASTRULATION
Transform bilaminar disc into trilaminar disc
Bilaminar disc layers:
o Epiblast
o Hypoblast
Cells of epiblast move down through primitive streak
o Epiblast layer now called ectoderm
o Convert hypoblast into endoderm Figure 3: VEGF stimulates formation of heart tubes and
o Migrate to cranial area and form mesoderm pericardial cavities
(2) Lateral folding
Lateral folding of layers forms a tube
o Ectoderm layers fuse
Trilaminar disc layers: o Mesoderm layers fuse
o Endoderm o Heart tubes fuse → make 1 heart tube
o Mesoderm o Pericardial cavities fuse → make 1 pericardial cavity
o Ectoderm  Heart tube connected to pericardial cavity by
dorsal mesocardium
II) HEART TUBE
Figure 4: Lateral folding forms the heart tube, pericardial cavity

(red) and GI tract (green)
Figure 1: Superior view of embryo Heart tube layers
(A) CROSS SECTION o Inner layer: endocardium (from mesoderm)
o Outer layer: myocardium (from cardiomyocytes)
3 types of mesoderm  Secrete jelly-like connective tissue between
o Paraxial mesoderm (next to notochord) endocardium and myocardium
o Intermediate mesoderm
o Lateral mesoderm
 Somatic layer
 Splanchnic layer
Heart tube develops from splanchnic layer of lateral
mesoderm
Figure 2: Mesoderm is divided into 3 types
Development of the heart EMBRYOLOGY: Note #1. 1 of 11

(B) SAGITTAL SECTION Blood enters from bottom
Leaves on top through outflow tracts (dorsal aorta, from
Accumulation of mesoderm in cranial part
aortic sack on truncus arteriosus)
Cardiogenic mesoderm connected to ectoderm and (1) Divisions

endoderm by: Divisions → structure which they form later
o Buccopharyngeal membrane o Truncus arteriosus (T.A.)
o Bulbus cordis (B.C.)
o Primitive ventricle (P.V.)
o Primitive atria (P.A) → left + right atrium

o Sinus venosus (S.V.): right and left horn with right
and left inflow tracks:
 Common cardinal veins (outside)
Figure 5: Mesoderm connected to ectoderm and endoderm,  Umbilical veins (middle)
stimulated by VEGF  Vitelline veins (inside)
(1) VEGF
Endoderm releases VEGF
o Forms heart tubes and pericardial cavities
Figure 6: Heart tube and pericardial cavity formed

(2) Cranio-caudal folding
Ectoderm and endoderm start folding
o Pull mesoderm toward neck area
o Pushes heart into chest cavity
o Heart tube moves into pericardial cavity
Figure 10: Heart tube divisions
III) CARDIAC LOOPING

Heart tube changes into shape of the heart
Happens inside pericardial cavity
Depends on dynein proteins
o If absent: kartagener syndrome with dextrocardia or
Figure 7: Cranio-caudal folding pushes heart into chest cavity situs inversus
 Dextrocardia: heart towards right side of body
(instead left)
 Situs inversus: all internal organs on opposite side
of body
(i) 1. step:
Figure 8: Heart tube moves into pericardial cavity
Truncus arteriosus + Bulbus cordis move down and to the
right
(C) HEART TUBE
Figure 11: Heart tube starts to fold
Figure 9: Heart tube

2 of 11 EMBRYOLOGY: Note #1. Development of the heart
(ii) 2. step: IV) SEPTA AND A-V VALVES
Truncus arteriosus + Bulbus cordis further move down
(A) SEPTA
and to the right
Primitive ventricle (P.V.) moves up and to the left (1) Development
Primitive atria (P.A.) move back and up
Separate atria and ventricles from one another
Goal: form atrioventricular (A-V) canal on both sides
(canal connecting atria and ventricles)
Between P.V. and P.A. is sulcus: atrioventricular sulcus
Figure 15: Cross section through A-V-sulcus

Neural crest cells move into heart tube → form posterior
Figure 12: Frontal and side view of cardiac folding and anterior endocardial cushion
Endocardial cushions grow towards each other and fuse
(iii) 3. step:
Primitive atria (P.A.) move on top of primitive ventricle
Septum intermedium: separates right from left A-V-canal
(P.V.) and bulbus cordis (B.C.)
Figure 16: Septum intermedium separates right from left A-V-

Figure 13: P.A. move on top of primitive heart during cardiac canal
folding
(B) ATRIOVENTRICULAR VALVES
Cells move from sinus venosus (S.V.)
o Into pericardial cavity and form a layer around heart (1) Development
Endocardial cells form valves
o Into heart
Connect valves: by annulus ring
Chordae tendineae develop from valve flaps
Valve between P.A. and P.V. → mitral valve
Valve between P.A. and B.C. → tricuspid valve
Figure 17: Atrioventricular valves form (coronal section)

(2) Function of valves
Provide one-way flow
Figure 14: Formation of pericardium and primitive conduction Prevent back flow through chambers
system

V) HEART CHAMBERS (B) VENTRICLES
(1) Development
(A) ATRIA
Coming from apex, a tissue grows upwards
(1) Development
Septum primum forms from top down towards septum Coming from septum intermedium, a tissue grows down
intermedium
But doesn’t reach septum intermedium → gap / hole
Primitive ventricle (P.V.) forms left ventricle

Bulbus cordis (B.C.) right ventricle
Figure 18: Ostium primum remains after between septum

primum and septum intermedium
Septum primum grows until it reaches septum
intermedium
Hole in septum primum develops towards top
Figure 21: Ventricles are formed by development of

interventricular septum
(2) Defects
If tissues don’t meet → hole in septum
Figure 19: Ostium secundum develops in septum primum VI) INFLOW AND OUTFLOW TRACKS
Septum secundum forms next to septum primum to
(A) INFLOW TRACTS
block the ostium secundum → remaining passage
Sinus venosus (S.V.) has 2 horns: right and left horn
Each horn has 3 veins:
o Common cardiac v.
o Umbilical v.
o Vitelline v.
(1) Development
Left horn:
o veins break down → no veins left
Right horn:
Figure 20: Septum secundum covers ostium secundum, only o umbilical vein degenerates → common cardinal and
small passage remains - foramen ovale vitelline vein remain
(2) Foramen ovale Left horn shifts to the right → fuses to right horn
Normal path of blood flow:
o RA → RV → pulmonary circulation → LA → LV Right common cardinal vein shifts upwards
→ systemic circulation
Embryo/fetus path of blood flow Right vitelline vein shift downwards
o RA → bypasses RV, directly goes to LA → LV
→ systemic circulation Left horn becomes → coronary sinus
Why? Inflow tracks to RA formed!
o In uterus no need for pulmonary circulation, baby
doesn’t breathe air by lungs → lungs can be skipped
in circulation
Eventually foramen ovale will close
(3) Defects
Patent foramen ovale

Open foramen, also in adulthood
Blood clots formed in systemic circulation (i.e. due
to DVT) are transported to RA
Pass through foramen ovale → LA → LV → enter
systemic circulation as “paradoxical embolism”
→ can cause stroke
Figure 22: Veins of right horn of S.V. form inflow tracks to RA
(B) OUTFLOW TRACKS (2) Rotation
(1) Aortic-pulmonary septum Aortic-pulmonary-trunk rotates

Rotation splits structures into separate aortic arch +
In truncus arteriosus and part of bulbus cordis pulmonary trunk
Neural crest cells migrate to this area Blood flow: follow same path as their blood flow along
In T.A.: aortic-pulmonary septum
o On right + left wall form truncal ridges o Aortic arch:
In B.C.:  Starts underneath pulmonary trunk
o On right + left wall form bulbar ridges  Leaves above
On top part of B.C. towards T.A. (in conus cordis) o Pulmonary trunk:
o On anterior + posterior wall form ridges  Starts above aortic arch
 Continues underneath
Figure 23: Ridges fuse in T.A and B.C.

Paired ridges approach each other and fuse Figure 25: Aortic arch and pulmonary trunk formed
o Truncal ridges → truncal septum
o Bulbar ridges → bulbar septum VII) SEMILUNAR VALVES
o Conus ridges → conus septum
Neural crest cells form 4 cushions:
Septa connect o Right, left, anterior, posterior
During rotation of aortic-pulmonary-trunk happens:
Aortic-pulmonary septum has a spiral shape around
central axis (corkscrew) due to position of truncal ridges
in conus cordis
Function: separate aortic arch from pulmonary trunk
Left ventricular outflow tract, for aorta
Right ventricular outflow tract, for pulmonary trunk
Figure 26: Cross section at junction of B.C. and conus cordis
Figure 24: Aortic-pulmonary septum with spiral shape

Blood flow:
o To aortic arch Figure 27: Posterior opening moved right, anterior opening left
 Blood flow from LV moves posteriorly of bulbar
septum
 Spiral upwards
 Leaves the trunk anteriorly of truncal septum
o To pulmonary trunk
 Blood from RC moves anteriorly of bulbar septum
 Spiral upwards
 Leaves the trunk posteriorly of truncal septum

VIII) APPENDIX
Figure 28: Formation of the heart tube – overview

Figure 29: Cardiac looping – overview

Figure 30: Formation of heart chambers, atrioventricular valves and septa – overview

Figure 31: Formation of aortic arch, pulmonary trunk and semilunar valves - overview

Figure 32: Development of the heart - overview

1) Which cells form the cardiac tissue?
a) Endoderm
b) Mesoderm
c) Ectoderm
d) Neural crest cells
2) Which part of the heart tube moves back and on top
of the B.C. and P.V.?
a) Truncus arteriosus
b) Primitive ventricle
c) Primitive atrium
d) Sinus venosus
3) Which septum is formed first?
a) Septum primum
b) Septum secundum
c) Septum intermedium
d) Aortic-pulmonary septum
4) Which action leads to the final positioning of the
aortic arch and pulmonary trunk?
a) Rotation
b) Stretching
c) Flexion
d) Division
5) The superior vena cava develops from:
a) The right horn
b) The left horn
c) The truncus arteriosus
d) The bulbus cordis
6) When is the primitive conduction system developed?
a) As soon as the heart tube is formed
b) After the heart valves are formed
c) After the cardiac looping
d) At the end of the heart development
CHECK YOUR ANSWERS

7. DEVELOPMENT OF THE PLACENTA

Embryology | Development of the Placenta Medical Editor: Ilia-Presiyan Georgiev
OUTLINE (3) The morula

turns into a blastocyst
I) PRE-IMPLANTATION Lots of water starts flowing into the morula
II) IMPLANTATION
o Forms a water-filled cavity - blastocoel
III) POST-IMPLANTATION
IV) MACROANATOMY The blastocyst consists of
V) FUNCTIONS o Blastocoel
VI) APPENDIX o Outer cell mass
VII) REVIEW QUESTIONS  Will form the trophoblast
VIII) REFRENCES • Will form the placenta
o Inner cell mass
 Will form the embryoblast
I) PRE-IMPLANTATION • Will form the endoderm, mesoderm and
ectoderm that will form the entire structure of
(1) In the ampulla of the fallopian tube the fetus
there are sperm and secondary oocytes in metaphase
2
Their fusion forms the zygote
o Has a lining – zona pelucida
(2) The zygote
divides (cleaves) into 2 cells
o The two-cell stage
o The cells are surrounded by the zona pelucida
It cleaves again into 4 cells
o The four-cell stage Figure 2 A blastocyst.
It cleaves again into 8 cells II) IMPLANTATION
o The eight-cell stage
(1) The uterus lining
It cleaves again into 16 cells consists of
o The sixteen-cell stage o Endometrium
o Forms a hollow ball of cells – the morula o Myometrium
o The cells are surrounded by the zona pelucida o Perimetrium
(2) The endometrium
is divided into two:
Basal part
o Called decidua basalis
o Made up of stratum basalis cells undergone
decidualization
 Bigger cells
 Filled with glycogen
 Filled with lipids
 More sustainable for fertilization
Apical part
o Called decidua functionalis
o Made of the replication and proliferation of decidua
basalis
(3) The blastocyst

normally attaches to and invades the decidua functionalis
Invading other layers of the uterine lining leads to
complications
o Usually require the uterus to be taken out after giving
birth
Figure 1 Cleavage of the zygote.  Invading the decidua basalis - placenta acreta
 Invading the myometrium - placenta increta
 Invading the perimetrium - placenta percreta
DEVELOPMENT OF THE PLACENTA EMBRYOLOGY: Note #1. 1 of 6

Forms two types of attachment with the endometrium • Prevents the corpus luteum from becoming
corpus albicans and stimulates it to continue
(i) Loose attachment: to produce progesterone
 Microvilli • The uterine blood vessels are dependent on
• On the trophoblastic cells progesterone
 Pinopodes • If the concentration of progesterone decreases
• Protrude from the decidua functionalis → the vessels spasm
→ ischemia of the surrounding tissue
→ rupturing and sloughing off of the
endometrium lining
(2) The embryoblast
differentiates into:
o Bilaminar disc
 Epiblast
 Hypoblast
o Amniotic cavity
 Above the epiblast
o Primary yolk sac
 Bellow the hypoblast
Figure 3 Loose attachment.
(ii) Tight attachment

 Integrines
• Molecules expressed by the trophoblastic cells
 Selectins
• Contained in carbohydrates on the decidua
functionalis
• Sometimes covered with collagen
 Chemokines
• Released by the trophoblast
• Stabilize the strong connection
Figure 5 Week 1 development.
(B) DAY 9
(1) The syncytiotrophoblast
continues to invade trough the stromal tissue
o Forms spaces of stromal tissue between its
projections - lacunae
Releases proteolytic enzymes
o Break down the blood vessels lining
Figure 4 Tight attachment.
o Allow the blood to seep in the lacunae
These attachments allow the blastocyst to start invading
In result the lacunar spaces are filled with blood and
the stroma of the endometrium and complete the
become intervillous spaces
implantation
III) OST-IMPLANTATION
(A) WEEK 1
(1) The trophoblast
differentiates into
o Cytotrophoblast
 The cytotrophoblastic cells proliferate rapidly
 Their membranes break down
 The cytoplasm and the nuclei fuse with those of
other cells
 Form a big pool of protoplasm and numerous
nuclei without cell borders - the
syncytiotrophoblast
o Syncytiotrophoblast
 Releases hydrolytic enzymes
• Allow it to break the stromal tissue of the
endometrium and invade it Figure 6 Day 9 Development.
 Secretes Human Chorionic Gonadotropin
hormone (hCG)
2 of 6 EMBRYOLOGY: Note #7. DEVELOPMENT OF THE PLACENTA

(C) DAY 12 (E) WEEK 3
(1) The intervillous spaces (1) The somatopleuric extraembryonic mesoderm
increase in number and fill with more blood invades the primary villi made by cytotrophoblastic cells
o Forms a core inside them
(2) The hypoblast
o The villi are still surrounded by the
(and the primary yolk sac, according to some sources) syncytiotrophoblast
will start producing connective tissue - extraembryonic These villi are called secondary chorionic villi
mesoderm o Can be anchored and floating
Under the cytotrophoblast and above the amniotic
cavity/primary yolk sac
Later will form the chorion of the placenta
o The fetal part of the placenta
(F) WEEK 4
there is already an embryonic folding
The mesodermal cells start differentiating
Figure 7 Day 12 development. o Form capillaries
The chorionic plate (a thick part of the chorion) comes
(D) DAY 14
off the chorionic villi
(1) The extraembryonic mesoderm o Forms the chorionic frondosum
starts breaking down forming: The connecting stalk
o The extraembryonic coelom – an empty space o Forms the umbilical cord
 Between two layers of extraembryonic mesoderm o Connects the chorionic plate with the embryonic
 It will become the chorionic cavity folding
o The somatopleuric extraembryonic mesoderm
(1) In the umbilical cord
 The layer towards the trophoblast
o The splanchnopleuric extra embryonic mesoderm the mesodermal cells form three blood vessels
 The layer towards the amniotic cavity/the primary o One umbilical vein
yolk sac o Two umbilical arteries
o The connecting stalk – connects the two layers  Move out into the chorionic plate and connect to
the chorionic arteries
(2) The cytotrophoblastic cells  The chorionic arteries move up the chorionic villi
proliferate and form primary chorionic villi that: and eventually become cotyledonal arteries
o Penetrate the syncytiotrophoblast  The villi will become tertiary chorionic villas by
o Move out and surround the intervillous spaces week 4
o Form the outer cytotrophoblastic shell

(2) There is an exchange
between the tertiary chorionic villas and the maternal
blood in the intervillous spaces
o From the fetus to the mother
Figure 8 Day 14 development.  CO2 and breakdown products
o From the mother to the fetus
 Oxygen, nutrients, even pathogens
This remains the exchange system until week 20

(G) WEEK 4-8 IV) MACROANATOMY
(1) The tertiary villi
(1) The fetus
Branch out
is located inside the uterus
o Still completely covered by the cytotrophoblast and
It is connected to the uterine lining with the umbilical cord
the syncytiotrophoblast
o Has extraembryonic mesoderm
Purpose - to increase the surface area for exchange
(2) The amniotic membrane
is the layer closest to the fetus
(3) The chorion
is the next layer
o Chorionic fondosum – formed from the continuation
of the extraembryonic mesoderm in the umbilical cord
 The collective name of all chorionic villi
o Chorionic leave - a thin, flat membrane
 The part of the chorion facing the uterine cavity
 Has no extensive villi system
(4) The decidua
is the last layer
o Decidua basalis
 Interacts with the chorionic frondosum
 Both of them collectively form the placenta
o Decidua capsularis
Figure 11 Week 4-8 development.
 The part of the decidua facing the uterine cavity
o Decidua parietalis
(H) WEEK 16-20  The decidua where there is no fetal involvement
(1) Tissue from the decidual membrane Eventually, as the fetus grows, the decidua capsularis will
merge with the decidua parietalis and obliterate the entire
starts to branch in uterine cavity
o The branches are called placental septa
o They separate the tertiary villas into septations -
cotyledons
 Around 15-20 cotyledons
 Each consist of 2-3 tertiary villi
The decidual tissue in them swells up and fills up with
glycogen, lipids, etc.
Figure 14 Macroanatomy.
Figure 12 Week 16-20 development.
(I) WEEK 20 V) FUNCTIONS

(1) The cytotrophoblast
(A) METABOLIC FUNCTIONS
regresses
o Makes the exchange of substances more quick and (1) Gas exchange
more efficient is the primary metabolic function
o From the mother to the fetus
 Oxygen
o From the fetus to the mother
 CO2
(2) Nutrient delivery
Ways of delivery
o Simple diffusion
o Facilitated diffusion
o Active transport
 Different types
Types of nutrients
o Glucose
o Amino acids
o Fatty acids
o Water soluble vitamins
 B vitamins

(3) Natural passive immunity (B) PATHOGENS
is conferred by IgG antibodies (1) Different pathogens
The mother has already made antibodies against different
foreign antigens can be transported across the placenta
o Transfers them to the fetus through the placenta Most important is the TORCH series
o Toxoplasmosmosis
(4) Hemolytic disease of the fetus and newborn  Caused by toxoplasma gondii
A condition also known as Rhesus disease  Causes significant fetal defects and damage
A Rh negative mother that have had previously a Rh  Treatment
positive baby (or a spontaneous abortion of a Rh • Spiramycin if the fetus has not been affected
positive baby) has created IgG antibodies against the Rh yet
(Duffy) antigen • Combination of Pyrimethamine and
o The antibodies then destroy the blood cells that are Sulfadiazine if the fetus has already been
Rh positive affected
o Others
There is a medication called Rhogam  HIV
o An anti IgG antibody erected against the Rh antigens  Syphilis
o Given to the mother so the immunological reaction is  Hepatitis (especially hepatitis B)
blocked o Rubella
 The immunological reaction takes place when the  Can cause a lot of cardiac and congenital defects
placenta breaks away during the third phase of as well as hearing loss.
delivery o Cytomegalovirus (CMV)
• Some of the blood that is Rh positive can go o Herpes simplex virus type 2
into the mother’s circulation
Another danger that people should be aware nowadays is
If the mother is already alloimmunized the Zika virus as it can be transmitted vertically as well
o The baby’s middle cerebral artery blood flow is Bacteria like Listeria monocytogenes
checked o Comes from pasteurized products and lunch meats
 Done through a Doppler
 Velocity is calculated based upon fetal anemia Viruses are the biggest threat because of their ability to
easily cross the placental membrane.
(5) Waste removal
(C) HORMONAL FUNCTIONS
of a lot of different types of waste products
o Urea (1) Estrogen and progesterone
o Uric acid, etc. Generally produced around 10th -12th week
Take over for the corpus luteum secretion during the rest
pregnancy
Make the endometrial lining thicken up
o Increasing the vasculature
o Provide a nutritive environment
Increase secretion
o Plugs up the cervix with a mucus plug
o Prevent external environment factors from harming
the fetus
Play a crucial role in the development of the fetus
(2) Thyroid hormone
Promotes the development of the central nervous
system
Lack of thyroid hormone can lead to cretinism
o Incomplete development of the CNS
o Can lead to mental retardation
(3) Human placental lactogen
Figure 15 Metabolic functions of the placenta.
Decreases the insulin release from the pancreas
Acts on the mother’s cells
o Promotes lipolysis
 Provides fatty acids for the baby
o Promotes gluconeogenesis
 Provides glucose for the baby
o Increases the cells insulin resistance
 So it can’t shuttle the glucose into the mom’s cells
(4) Relaxin
Relaxes (increases the laxity of) specific ligaments of the
pubic symphysis
o The pelvic inlet and outlet are widened out
o Ensure easier passage of the baby

(5) Corticotrophin-releasing hormone VI) REVIEW QUESTIONS
In addition to the mother’s pituitary gland
What is the name of the ball of cells formed in the
Stimulates adrenocorticotropic hormone (ACTH)
16-cell stage of cleaving?
production
a. Zygote
o Stimulates cortisol production
b. Morula
Cortisol plays an important role in lung development and c. Blastocyst
surfactant production d. Blastocoel
If the baby is born prematurely (before 34 week) there is
not enough cortisol Which is a part of the blastocyst?
→ not enough surfactant a. Blastocoel
→ the alveoli of the baby will be collapsed b. Trophoblast
→ it is almost impossible for the baby to get enough c. Embryoblast
strength through the diaphragm and the intercostal d. Primary yolk sac
muscles to pull air in and pop the alveoli open
This leads to infant respiratory distress syndrome Which does not take part in forming a tight
attachment?
a. Integrines
b. Selectins
c. Chemokines
d. Microvilli
Which hormone does the syncytiotrophoblast

secrete?
a. Progesterone
b. Adrenocorticotropic hormone
c. Human Chorionic Gonadotropin hormone
d. Estrogen
Figure 16 Hormonal functions of the placenta. Which week do primary chorionic villi develop?
a. 1
b. 2
c. 3
d. 4
When do cotyledons form?

a. Week 4
b. Week 4-8
c. Week 16-20
d. Week 20
Which layer of the placenta regresses during week

20?
a. Chorion
b. Syncytiotrophoblast
c. Amniotic membrane
d. Cytotrophoblast
Which part of the decidua has no fetal involvement?

a. Decidua basalis
b. Decidua functionalis
c. Decidua capsularis
d. Decidua parietalis
Which medication is not given for toxoplasmosis?

a. Rhogam
b. Spiramycin
c. Pyrimethamine
d. Sulfadiazine
Which hormone is not produced by the placenta

a. Thyroid hormone
b. Human placental lactogen
c. Human Chorionic Gonadotropin hormone
d. Corticotrophin-releasing hormone
CHECK YOUR ANSWERS

14. DEVELOPMENT OF THE RESPIRATORY SYSTEM

Embryology | Development of the Respiratory System Medical Editor: Aldrich Christiandy
Trilaminar disc looks like a pancake and we want to fold

OUTLINE o Fold this pancake into two directions (view from cross
section)
I) FUNDAMENTALS  Lateral folding
II) DEVELOPMENT OF THE RESPIRATORY SYSTEM
• Fold in a lateral type of way and bring them
III) APPENDIX
IV) REVIEW QUESTIONS together
V) REFERENCES  Craniocaudal folding
• Pull out from the top of the embryo or cranial
portion and going back to the caudal portion
(B) FOLDING OF TRILAMINAR DISC
I) FUNDAMENTALS
We develop the respiratory system from two germ layers:
o Endoderm
o Mesoderm
Gastrulation is a process where bilaminar disc →
trilaminar disc
o There’s quick folding process in both lateral folding
process and craniocaudal folding process
 Some of the structures that are developing from
these layers
• Larynx
• Trachea
• Lungs
(A) BILAMINAR DISC – WEEK 2

Figure 2. Folding of trilaminar disc
Endoderm and mesoderm make your respiratory system
Endoderm is going to give way to gut tube (the epithelial
lining and the gland of GI tract)
o Epithelial lining of the respiratory tract (larynx,
trachea, lung)
Mesoderm closest to the neural tube is called paraxial
mesoderm
A bit more lateral is your intermediate mesoderm
The one closest to the ectoderm called somatic layer of
the lateral plate mesoderm
Closest to the endoderm or the gut tube is going to be
Figure 1. Gastrulation of embryo splanchnic layer of lateral plate mesoderm
We made up of our epiblast layer on the top o Gives rise to cartilage, muscle, connective tissue
o Above epiblast is amniotic cavity around the larynx, trachea, lungs
o Below epiblast is hypoblast layer
 Below hypoblast layer is yolk sac layer Table 1. Derivatives of the layer of embryo
Layers Derivative Structures
We develop a nice primitive streak in the epiblast layer
o Some epiblast cells move through the primitive Mesoderm
streak Around the larynx,
 Convert the hypoblast layer → new endoderm trachea, and lungs
Splanchnic layer of the
layer lateral plate mesoderm Cartilage
o More epiblast cells move through primitive streak Muscle
 It forms a new layer between these new endoderm Connective tissue
→ mesoderm Epithelial lining of the
Endoderm
Notochord → epiblast cells moving through the primitive respiratory tract
node
o And then go through the process called neurulation
and make a structure called neural tube
Epiblast cell start differentiating themselves and
turning into ectoderm
This is called gastrulation
o Take bilaminar disc and turn into a trilaminar disc
Notogenesis is also occurring
DEVELOPMENT OF THE RESPIRATORY SYSTEM EMBRYOLOGY: Note #14. 1 of 7

(C) CRANIOCAUDAL FOLDING OF TRILAMINAR II) DEVELOPMENT OF THE RESPIRATORY SYSTEM
DISC
(A) LARYNX
Figure 3. Derivatives of endoderm and splanchnic layers of

lateral plate mesoderm
Sagittal view after craniocaudal folding
o Three portions from endoderm and splanchnic
layers of the lateral plate
 Foregut Figure 4.Pharyngeal apparatus
 Midgut
We have foregut, midgut, hindgut, pharyngeal apparatus
 Hindgut
Let’s take a little section, take a look at the layer of
o Little pouches that are part of the pharyngeal
apparatus pharyngeal apparatus
 Pharyngeal apparatus comes from primitive o Buccopharyngeal membrane → become mouth
pharynx o Inner portion → endoderm (part of pharyngeal
pouches)
o Endoderm and splanchnic layers of the lateral plate
 Makes the epithelium and the glands of the
Larynx larynx
o Endoderm o Next layer is mesoderm (part of pharyngeal arch)
 Coming from a structure called 4th and 6th  Makes muscle, connective tissue, cartilage
pharyngeal pouches  We have 1st, 2nd, 3rd, 4th, and 6th pharyngeal
 Gives rise to the epithelial lining of the larynx arches
o Mesoderm • Sometimes 5th pharyngeal arch either
 Coming from a structure called 4th and 6th develops or digresses or doesn’t develop at
mesoderm part of pharyngeal arches all
Trachea o Ectoderm (part of pharyngeal clefts)
o Endoderm Portion of the pharyngeal apparatus that is actually
 Coming from the foregut (buds off the foregut) making the larynx → 4th and 6th pharyngeal arch
o Mesoderm
 Lateral plate mesoderm (splanchnic layer of the (1) Week 5
lateral plate mesoderm) Develop a little cavity → laryngeal orifice
Lungs Within the orifice, some of the endodermal tissue within
o Endoderm pharyngeal pouches start invading into the laryngeal
 Foregut orifice
o Mesoderm o It makes vocal cord
 Lateral plate mesoderm (splanchnic layer of the
(2) Week 6
lateral plate mesoderm)
Mesoderm starts forming cartilage, muscles that are
We have to make the larynx first → then trachea → and
surrounding the portion of the larynx
then the lungs
Start developing swellings around the orifice
o One of the swellings develop on the top of the
Table 2. Respiratory system and the origin
laryngeal orifice → epiglottic swelling
Respiratory
Origin o Below develops another swelling →arytenoid
System
swelling
4th and 6th pharyngeal
Endoderm pouches Over time the mesoderm continues to make more
Larynx th th cartilage
4 and 6 mesoderm
Mesoderm part of pharyngeal arches o Endoderm continues invade to laryngeal orifice
o Help pharyngeal pouches to make a nice little
Endoderm Foregut epithelial lining of larynx
Trachea Splanchnic layer of the
Mesoderm
Endoderm Foregut
Lungs Splanchnic layer of the
Mesoderm
2 of 7 EMBRYOLOGY: Note #14. DEVELOPMENT OF THE RESPIRATORY SYSTEM

(3) Week 6 – 12 (B) TRACHEA AND LUNGS
Figure 5. Week 6 – 12 developments of mature larynx

We want to make mature larynx
Along the way, we develop some things
o Endoderm give way to the epithelium lining of the Figure 6. Formation of lung bud from foregut
larynx
 Pseudostratified ciliated columnar epithelial We have a nice good old sagittal section
tissue o We have foregut, midgut, hindgut, pharyngeal
 Vocal cords apparatus
 Laryngeal orifice becomes laryngeal inlet Take a portion of the foregut
o Mesoderm o Side and front view
 Laryngeal cartilage → thyroid, cricoid, arytenoid o What is happening?
cartilage, cuneiform cartilage, corniculate  Foregut is helping us to develop our trachea and
cartilage lung
 Laryngeal muscles → cricoarytenoids,
cricothyroid muscles (1) Week 5
 Nerve that supplies down the larynx muscles
(vagus nerve)
• Also derived from the 4th and 6th pharyngeal
arches, supplying the laryngeal muscles
Table 3. Week 5 derived structures of larynx

Layers Derivative Structures
Laryngeal cartilage → thyroid,

cricoid, arytenoid cartilage,
cuneiform cartilage,
corniculate cartilage
Mesoderm Laryngeal muscles →

cricoarytenoids, cricothyroid
muscles
Nerve that supplies down the

larynx muscles (vagus nerve)
Epithelial lining of the larynx Figure 7. Lung development during week 5
Pseudostratified ciliated Some of the endodermal cells start coming out and
columnar epithelial tissue budding off of the foregut → lung bud (From the side
Endoderm Vocal cords view)
Laryngeal orifice becomes o Frontal view or anterior view
laryngeal inlet  Some of the endodermal cells come out into the
bud and create a long bud
 It creates a little groove that goes into the anterior
lung bud → tracheoesophageal groove/ridge
(4) Week 12
Which structure that is wrapping around the gut tube?
Now we have mature larynx Mesoderm
o Laryngeal orifice → laryngeal inlet o Which part of mesoderm? Lateral plate mesoderm
o Epiglottic folds  Splanchnic layer of the lateral plate mesoderm →
o Cartilage made from the mesoderm cartilage, connective tissue and muscle
o Muscle from the cricoarytenoid, cricothyroid
o Vagus nerve supplying muscles → penetrate through Endoderm become epithelial lining of the tracheal lung
here and give sensory information to the actual Lung bud creates bifurcation → bronchial bud
laryngeal epithelium

(3) Canalicular stage
Tracheoesophageal grooves/ridges come together and
meet in the middle
o They form nice little septum between the anterior
lung bud and posterior foregut (which becomes
esophagus) → tracheoesophageal septum
 It helps us to separate the foregut right from the
diverticulum coming off of it
 Diverticulum will become the trachea
• Anterior to the esophagus
 Tracheoesophageal septum will completely
close and separate posteriorly Figure 9. Canalicular stage
Lung bud continue to grow and create a nice separation Continues at week 16 to about week 26
o Anteriorly we’ll going to have lung bud → trachea We take our terminal bronchial
and eventually lungs o Terminal bronchial will make neck structures called
o Posteriorly is going to make foregut, in this case respiratory bronchial
going to become the esophagus
Respiratory bronchial breaks off into smaller things called
Endoderm which came from the actual gut tube will alveolar ducts (3-6 alveolar ducts each respiratory
invade into the lung bud and bronchial bud bronchial)
o This makes epithelium and glands o They feed into primitive alveoli
Lateral plate mesoderm → muscle (bronchial smooth o They’re made up of cuboidal cells
muscle, trachealis muscle), connective tissue, cartilage  Not good for gas exchange because too thick
Completely separate the anterior lung bud from the o They’re not very good at their job yet
posterior foregut tube Some pulmonary capillaries start kind of growing here
o Foregut tube will become esophagus around the primitive alveoli
Zoom into the primitive alveoli
(2) Pseudo-glandular stage
o It’s very immature, it’s only cuboidal cells →
immature primitive alveoli that are formed at the end
of canalicular stage
o Cuboidal cells are not good at gas exchange
 ↓ activity for gas exchange process
o Next stage is to make some of them smaller
 So that they’ll be easier for that gas exchange
process to occur
(4) Saccular stage
Figure 8. Pseudo-glandular stage

We developed the lung bud, bronchial buds and
separation of the developing lung away from the foregut
In this stage, we continue to build from these bronchial
buds Figure 10. Saccular stage
o Starts around week 5 and continues to occur until Happens around week 26 → birth
about week 16 ↑ the number of alveoli, ↑ numbers of respiratory
As bronchial bud grows, the first thing they’re going to bronchioles
make is these left and right primary bronchi Basement membrane forms around the primitive alveoli
Primary bronchi are going to split o Consists of four structures [Tortora et.al.,2017]
o Remember, within the adult lung, generally you have  Alveolar wall
about three lobes in the right lung and two lobes • Type I and type II alveolar cells
in the left lung • Associated alveolar macrophages (dust cells)
o Primary bronchi are going to split into lobar bronchi  Epithelial basement membrane
 Three lobar or secondary bronchi on the right  Capillary basement membrane
 Two lobar or secondary bronchi on the left  Capillary endothelium
Secondary bronchi break up even more into a structure ↑ number of pulmonary capillaries
called tertiary bronchi Alveoli is starting to be more mature
o 20 tertiary bronchi on the right o All cuboidal → 2 different types of cells
o 18 tertiary bronchi on the left  Flat cells → Type I pneumocytes
Tertiary bronchi feed into even smaller bronchi → • Gas exchange occurs
terminal bronchioles • O2 moves occurs across the cell, CO2 move
across the cell

 Cuboidal cells → Type II pneumocytes (more (i) Before birth process
specialized) o Birth does have a little bit of fetal breathing movement
• Make a kind of protein and lipid complex that  Purpose to allow for the lung and the muscle of
coats the inner surface of the alveolar the respiratory system to kind of work one another
membrane → surfactant  Baby breathes in amniotic fluid
• Surfactant prevents alveoli from collapsing,  Amniotic fluid from the amnion will actually come
keeps them open, reducing surface tension into baby’s alveoli and cover all of the area of
• Alveoli naturally wants to collapse alveoli
• It’s really hard for the baby to bring in air • Allow the lung and muscle to work together →
because it has to pop open, already collapsed strengthen baby’s lung
alveoli  Bringing in air from the first cry
(5) Alveolar stage (ii) At the time of birth,
amniotic fluid gets sucked up into the pulmonary capillary
o Type II secretes surfactant
o Surfactant helps to reduce surface tension and keep
those alveoli open
o If the baby is born premature (e.g., week 26, 27),
baby doesn’t have time to really produce surfactant
 Surfactant decrease, surface tension increase,
collapsing pressure increase
(iii) When the baby is born,
take in its first breath → push the amniotic fluid to
pulmonary capillary → leave a layer of surfactant, layer of
surfactant is thin
o Because of that, alveolar collapse
o Whenever it tries to breath, it has to take in so much
more air to open the closed alveoli
o This is called infant respiratory distress syndrome
 ↓↓ surfactant production
o Baby takes air in → amniotic fluid gets absorbed,
Figure 11. Alveolar stage
surfactant layer remains
Generally, this starts around week 36 (occurs around the  This helps to reduce surface tension to allow the
same time as saccular stage) baby to breathe and take in air without a lot of
o But extend very far past birth → 8 years of age effort
Type I + Type II alveolar cells
o ↑ number of alveoli
o Form a septum (or partition) within the alveoli → to
increase the surface area
 Contributes to maturation process
Thickening of basement membrane
↑ number of pulmonary capillaries
Around birth start off with approximately close to 100
million of alveoli → Increase the number of alveoli to
about 300 million at year of 8
Figure 13. Infant respiratory distress syndrome [Dr. Jeremy J., 2013]
Prematurely born babies (< 34th week [e.g., 31st week])
aren’t able to produce enough surfactant → infant
respiratory distress syndrome (IRDS) / neonatal
respiratory distress syndrome
o Hard for baby to expand the alveoli due to ↑ surface
tension
 Collapsing of the alveoli creates unequal alveoli
 Have to put the baby on a mechanical ventilator to
push air into the baby
When the baby is form and the umbilical cord is cut → ↓ O2
level inside baby
o This triggers hypoxia → activates respiratory centers
inside baby
 Activates some of the muscle → contraction to bring
air in → baby’s first cry
 But, when the baby has IRDS, they can’t bring the air
in due to alveoli don’t want to open
• Takes so much energy and work to open the
alveoli → hard time for breathing
Figure 12. Baby breathing process o Baby go into distress and need to be put on
the ventilator

III) APPENDIX
Table 4. Summary of lung development stages

Stages Overall Process Diagram Notable Processes
Endodermal cells coming out and
budding off of foregut →
Lung bud creates bifurcation →
bronchial bud
Endodermal cells come into the bud and

create a little groove that goes into the
anterior lung bud →
Week 5 tracheoesophageal groove/ridge
o They will form transesophageal
septum
Diverticulum → trachea
o Anterior to the esophagus
Primary bronchi are going to split into

lobar bronchi
o Three lobar or secondary bronchi on
the right
o Two lobar or secondary bronchi on
the left
Secondary bronchi break up even
Pseudoglandular more into a structure called tertiary
stage bronchi
(Week 5) o 20 tertiary bronchi on the right
o 18 tertiary bronchi on the left
Tertiary bronchi feed into even smaller
bronchi → terminal bronchioles
Terminal bronchial → respiratory

bronchial
Respiratory bronchial → alveolar ducts
o They feed into primitive alveoli
o They’re made up of cuboidal cells
 Not good for gas exchange
because too thick
Canalicular stage Some pulmonary capillaries growing
(Week 16 –26) around the primitive alveoli
Primitive alveoli (immature)
o Formed at the end of canalicular
stage
o It’s very immature, it’s only cuboidal
cells
 Cuboidal cells are not good at
gas exchange
↑ the number of alveoli, ↑ numbers of
respiratory bronchioles
Basement membrane forms around the
primitive alveoli
↑ number of pulmonary capillaries
Saccular stage All cuboidal → 2 different types of cells
(Week 26 → birth) o Flat cells → Type I pneumocytes
 Gas exchange occurs
 O2 moves occurs across the cell,
CO2 move across the cell
o Cuboidal cells → Type II
pneumocytes (more specialized)
 Make surfactant

Type I + Type II alveolar cells
o ↑ number of alveoli
o Form a septum (or partition) within
the alveoli → to increase the
surface area
 Contributes to maturation
process
Alveolar stage Thickening of basement membrane
(Week 36 → 8 ↑ number of pulmonary capillaries
years of age) Around birth start off with approximately
close to 100 million of alveoli →
Increase the number of alveoli to about
300 million at year of 8
Which stage that involves the development two

IV) REVIEW QUESTIONS types of pneumocytes?
a. Pseudo-glandular stage
Where does epiblast cells move through in order to
b. Canalicular stage
form mesoderm and endoderm layers?
c. Saccular stage
a. Primitive streak
d. Alveolar stage
b. Notochord
c. Neural crest
What’s the function of septum within the alveoli
d. Yolk sac
that’s formed during alveolar stage?
a. Decrease surface area of the alveoli
Which parts does the splanchnic layer of lateral
b. Increase surface area of the alveoli
plate mesoderm give rise to?
c. Decrease volume of the alveoli
a. Cartilage
d. Decrease the thickness of the alveoli membrane
b. Muscle
c. Connective tissue
d. All of above Which condition that occurs in premature baby
where the baby can’t produce enough surfactant?
Where does the endoderm of larynx come from? a. Pneumonia
a. 1st pharyngeal pouches only b. Atelectasis
b. 4th and 6th pharyngeal pouches c. Acute respiratory distress syndrome
c. 4th and 6th mesoderm part of pharyngeal arches d. Infant respiratory distress syndrome
d. 5th pharyngeal arch only
CHECK YOUR ANSWERS
Which structure that buccopharyngeal membrane V) REFERENCES

gives rise to? ● Sadler TW. Langman's Medical Embryology. Philadelphia:
a. Mouth Wolters Kluwer; 2019.
b. Larynx ● Le T. First Aid for the USMLE Step 1 2020. 30th anniversary
c. Esophagus ● Marieb EN, Hoehn K. Anatomy & Physiology. Hoboken, NJ:
d. Trachea Pearson; 2020.
● Boron WF, Boulpaep EL. Medical Physiology.; 2017.
● Moore, K., Persaud, T., & Torchia, M. (2016). The Developing
Which structure that laryngeal orifice gives rise to? Human: Clinically Oriented Embryology. Philadelphia: Elsevier.
a. Lungs ● Tortora, G. J., Derrickson, B., & John Wiley & Sons, (2017).
Principles of anatomy & physiology.
b. Trachea ● Case courtesy of Dr Jeremy Jones, <a
c. Vocal cord href="https://radiopaedia.org/">Radiopaedia.org</a>. From the case
d. Nose <a href="https://radiopaedia.org/cases/23921">rID: 23921</a>
Vagus nerve that supplies the larynx muscle derived

from which structure?
a. 4th and 5th pharyngeal arches
b. 4th and 6th pharyngeal arches
c. 5th pharyngeal arch only
d. 4th pharyngeal arch only
Which stage that involves the development of

primary bronchi to lobar bronchi?
a. Pseudo-glandular stage
b. Canalicular stage
c. Saccular stage
d. Alveolar stage

1. DEVELOPMENT OF THE URINARY SYSTEM

Embryology | Development of the Urinary System Medical Editor: Aldrich Christiandy
I) OUTLINE
II) FUNDAMENTALS
III) DEVELOPMENT OF THE URINARY SYSTEM
IV) APPENDIX
V) REVIEW QUESTIONS
VI) REFERENCES
II) FUNDAMENTALS
Figure 1.2. Embryo after gastrulation and condensation of

mesoderm
• Folding the trilaminar disc

Craniocaudal folding
Lateral folding
o Once the intermediate mesoderm is formed
 It starts to really condense near the splanchnic
layer of the lateral plate mesoderm
Figure 1.1. Embryo before folding • It makes a little divot
 Condensation of the intermediate mesoderm, kind
• Basic foundation of bulging in
Intermediate mesoderm  It creates like a little divot by the big chunk of
How do we make intermediate mesoderm and make the mesoderm → urogenital ridge
urinary system?  Core of the mesoderm which part of the urogenital
ridge → nephrogenic cord
• Bilaminar disc  Urogenital ridge → urinary system, reproductive
Layers from top to bottom system
o Amniotic cavity We’re going to focus on the portion of the urogenital
o Epiblast ridge which is going to be nephrogenic cord
o Hypoblast
o Yolk sac III) DEVELOPMENT OF THE URINARY SYSTEM
• We develop a little cavity or little place called (A) NEPHROGENIC CORD AND PRONEPHROS
primitive streak
Epiblast cells move through primitive streak
o Take hypoblast and turn it into a new layer →
endoderm
o It makes a new layer above the endoderm →
mesoderm
o Epiblast cell differentiate themselves and turn into
ectoderm
o This turns into trilaminar disc → gastrulation
• Mesoderm components
Paraxial mesoderm
Intermediate mesoderm
Lateral plate mesoderm Figure 1.3. Sagittal view of nephrogenic cord and cloaca
o Somatic layer
o Splanchnic layer (1) Nephrogenic cord
Gut tube is located anteriorly to the nephrogenic cord
Important portion of gut tube (cloaca) become
o Anal canal
o Bladder
o Urethra
Nephrogenic cord → urinary system
DEVELOPMENT OF THE URINARY SYSTEM EMBRYOLOGY: Note #15. 1 of 7

(2) Week 4 (1) Glomeruli formation
Figure 1.6 Glomeruli formation

Mesonephric tubules continue to keep growing from
mesonephric duct
There’s a structure located between gut tube and
nephrogenic cord
Figure 1.4. Week 4 - Pronephros development
o We see vascular structure called aorta
Cervical region of the nephrogenic cord o Aorta and mesonephric tubule start meeting one
o Development of pronephros another, forming a structure from aorta via
 It will actually digress a bit later angiogenesis called glomeruli (little capillary
Pronephros is made out of two parts: structures that come from angiogenesis)
o Duct  When we have a vessel that we’ve already formed
o Little tubules that form in front of it called and starts making new vessel off it →
nephrotome angiogenesis process
(3) Week 5 Form little capsules around the primitive glomerulus

(primitive urinary system)
Pronephros starts digressing and degenerate by the o If we zoom it on, it forms a capsule like a bowman’s
end of week 4 capsule
o The purpose is unknown o Aorta having a bud off via angiogenesis process and
o It could be important because it helps providing a making a capillary that filled with blood
structure that the next part from the nephrogenic cord  Filter into the bowman capsule
derives o Blood run to aorta → it has to run through arterial
A structure starts to form at the end of week 4 that through glomerular capillaries then via filtration
develops off the pronephros → mesonephros process
o Pronephros develops in the cervical region  Some plasma, solute get filtered into the bowman
o Extends from the thoracic region to the lumbar capsule
region and connects with the cloaca  Then move down the mesonephric tubule into the
mesonephric duct → cloaca → drains urine
(B) MESONEPHROS
(2) Mesonephros and cloaca
Figure 1.7. Mesonephros and cloaca

Mesonephros → mesonephric duct connecting to the
cloaca.
o Mesonephric tubule forming bowman’s capsule
o Coming off of the aorta, angiogenic process making
the little glomeruli
Figure 1.5. Week 5 - Mesonephros development
o Filtering the plasma from the blood, moving through
Mesonephros components the bowman’s capsule through mesonephric tubule
o Mesonephric duct  Down the mesonephric ducts, emptying into the
o Mesonephric tubules (comes off mesonephric duct) cloaca
Mesonephros comes off of the degenerating pronephros Cloaca has two things
and forming from thoracic region to lumbar region o Mesonephric duct is dumping primitive urine → to the
(thoracolumbar region) cloaca
Mesonephros is going to become primitive urinary o Hindgut is making poop → to the cloaca
system o Draining these two structures to the allantois
Mesonephric duct is connected with cloaca → cloaca
become bladder and the urethra Primitive urinary system makes urine from about week 5
o Kidney and ureter will connect to the bladder and → week 10
urethra o Made up off mesonephros
2 of 7 EMBRYOLOGY: Note #15 DEVELOPMENT OF THE URINARY SYSTEM

(C) METANEPHROS (2) Renal pelvis formation
Figure 1.8. Metanephric mesoderm development

In the pelvic region, some intermediate mesoderm
starts of condensing in front of mesonephric duct →
metanephric mesoderm / metanephric blastema
o Forms in the pelvic region
Figure 1.11. Renal pelvis formation

Renal pelvis is going to bifurcate and form more
structure
It grows some little knobby are going to become
major calyx
Growth of major calyx will bud even more into minor
calyx
Figure 1.9. Reciprocal induction between metanephric Minor calyx will keep on growing more structures
blastema and ureteric bud → collecting tubules
(1) Metanephric blastema Ureteric stalk becomes ureter

Basically, we formed all of the collecting system for the
Starts releasing growth factors and stimulate the urinary system
mesonephric duct Mesonephros is still continuing to become our urinary
o It will make a little bud → ureteric bud system
o Ureteric bud will eventually make ureter (collecting
system)
Ureteric bud starts releasing more growth factors
o Stimulate metanephric blastema to grow bigger
Two-way interaction between these two structures
→ reciprocal induction
Figure 1.12. Metanephric mesoderm cap development
Figure 1.10. Ureteric bud and ureteric stalk

Ureteric bud grows and creates a nice stalk
→ ureteric stalk
Ureteric bud invades (grows inward into) the metanephric
blastema
o It creates a big tubular structure called renal pelvis

(3) Collecting tubules (4) Kidneys’ migration
Zoom into the collecting tubules and metanephric
mesoderm around it
Metanephric capping the collecting tubule
o Becomes metanephric mesoderm cap
Cells of the collecting tubule starts secreting growth
factors
o Influencing metanephric mesoderm cap
o Causes proliferation and condensing of metanephric
mesoderm cap
o Metanephric mesoderm cap → metanephric vesicle
o Continuous release of growth factor
o Metanephric vesicle starts kind of becoming S-
shaped (coiled) → metanephric tubule
Figure 1.14. Mature kidney ascension from pelvis region to

upper quadrant of abdomen
Take a look at portion of aorta at the level of common iliac
o Metanephros develop in the pelvic region
o Artery found in pelvic region is the common iliac
arteries
o The actually mature kidney develops in the pelvis
and ascend upward
From the common iliac, we have arterials and capillaries
→ create glomerular capillaries (interact with bowman’s
Figure 1.13. Development of DCT, PCT, and Bowman's capsule)
capsule o Bowman’s capsule developed from PCT, PCT
We’re going to have connection between collecting tubule developed from DCT, DCT is actually stimulated from
and metanephric tubule the collecting tubule
o Metanephric tubule becomes distal convoluted o Starts making urine because blood will move through
tubule (DCT) the iliac system through the glomerular capillaries
o We have proximal convoluted tubule (PCT)  And get filtered across this bowman’s capsule into
o It starts to make cup shaped called Bowman’s PCT → DCT
capsule  Goes into collecting tubule → drain to cloaca
Very similar to mesonephric tubules The metanephric mesoderm between PCT and DCT
starts grow downward and form a loop called loop of
Henle
We made the nephron from metanephric mesoderm and
collecting system from the ureteric bud
Common iliac arteries start degenerating
o Kidney start ascending (moving upwards) into the
upper quadrant of abdomen
o Aorta will develop lateral branches → renal arteries

(5) Week 10 Table 1. Separation of cloaca and derivatives
Anterior Posterior
Urogenital sinus Anal canal
Proximal Bladder
Urethra
Female → female
Middle urethra
Male → prostatic
urethra, membranous
urethra
Distal Penile urethra
Figure 1.15. Week 10 - Mesonephric duct and cloaca
Metanephros is taking over the function of mesonephros (7) Structure that drains cloaca
o Mesonephric duct draining urine from mesonephric
tubule before week 10
Cloaca getting urine from mesonephric duct and poop
from the hindgut → allantois
Connecting portion of ureter and mesonephric duct fuse
with the cloaca
Mesonephric duct moves a little bit backward;
o Ureter move a little bit more toward side
When they’re joining, creates a structure called vesicular
trigone
o (Represented at urethra)
Mesonephric duct will become
 Vas deferens
 Epididymis
 Seminal vesicle
 Common ejaculatory duct
 Uterus
(6) Cloaca development
Figure 1.17. Allantois development

Allantois drains cloaca
Allantois development
o Allantois → urachus → median umbilical ligament
Figure 16. Cloaca development

We have to make a cloaca like a bladder and urethra
Create a septum in between the cloaca→ urorectal
septum
(i) Urorectal septum

(a) Separate the cloaca into two distinct parts
Separate the cloaca into two distinct parts
Anterior portion
o Becomes urogenital sinus
 Becomes bladder and urethra
Posterior portion
o Anal canal
(b) Separate hindgut away from cloaca

Proximal portion of urogenital sinus
o Becomes bladder
Middle portion of urogenital sinus
o Becomes urethra
 Female → female urethra
 Male → prostatic urethra, membranous urethra
Distal portion of urogenital sinus
o Becomes penile urethra

IV) APPENDIX
Figure 1.18. Development of mature kidney [Moore et al, 2016]
Figure 1.19. Development of the urinary system [Tortora et al., 2018]

V) REVIEW QUESTIONS VI) REFERENCES
Which structure below that will digress during the ● Moore, K., Persaud, T., & Torchia, M. (2016). The Developing
Human: Clinically Oriented Embryology. Philadelphia: Elsevier.
development of nephron? ● Tortora, G. J., Derrickson, B., & John Wiley & Sons, (2017).
a. Glomerulus Principles of anatomy & physiology.
b. Pronephros ● Sadler TW. Langman's Medical Embryology. Philadelphia:
Wolters Kluwer; 2019.
c. Mesonephros ● Le T. First Aid for the USMLE Step 1 2020. 30th anniversary
d. Metanephros edition: McGraw Hill; 2020.
Where does the urine from mesonephric duct get ● Marieb EN, Hoehn K. Anatomy & Physiology. Hoboken, NJ:
Pearson; 2020.
drained into in the primitive urinary system? ● Boron WF, Boulpaep EL. Medical Physiology.; 2017.
a. Urogenital ridge
b. Cloaca
c. Allantois
d. Bowman’s capsule
Which structure that starts condensing in the

pelvic region that gives ride to metanephric
blastema?
a. Intermediate mesoderm
b. Paraxial mesoderm
c. Lateral plate mesoderm
d. Somatic layer of lateral plate mesoderm
Which structure that is formed due to invasion of

ureteric bud to the metanephric blastema?
a. Allantois
b. Cloaca
c. Renal pelvis
d. Ureter
What is the fate of ureteric stalk that is formed

when the ureteric bud grows?
a. It will digress
b. It will become anal canal
c. It will become collecting tubule
d. It will become ureter
Where does Bowman’s capsule come from when

the metanephros growth is in the process?
a. Collecting tubule
b. Distal convoluted tubule
c. Proximal convoluted tubule
d. Glomerulus
Where does metanephros develop?

a. Umbilical region
b. Epigastric region
c. Acral region
d. Pelvic region
Which lateral branches that aorta develop to make

connection with the matured kidney?
a. Renal arteries
b. Pelvic arteries
c. Common iliac arteries
d. Thoracic artery
Which structure that separates cloaca into two

distinct parts?
a. Urogenital sinus
b. Septum primum
c. Urorectal septum
d. Ostium primum
Which structure that cloaca’s anterior portion

will give rise to?
a. Anal canal
b. Bladder and urethra
c. Urogenital sinus
d. Umbilical ligament
CHECK YOUR ANSWERS

1. DEVELOPMENT OF VASCULAR SYSTEM

Development of Vascular System Medical Editor: Dr. Sofia Suhada M. Uzir
OUTLINE (B) VASCULOGENESIS

Development of blood vessels from mesoderm of
I) BLOOD VESSELS trilaminar disc within the embryo
II) THE HEART TUBE
Developmental process:
III) CROSS SECTION OF EMBRYO
IV) SYSTEMIC CIRCULATION (1) VEGF release
V) VENOUS CIRCULATION
VI) REVIEW QUESTIONS Endodermal tissue releases vascular endothelial growth
VII) REFERENCES factor (VEGF)
→ influence splanchnic layer of lateral plate to proliferate
and differentiate into specific types of tissue
I) BLOOD VESSELS
(2) Proliferation and differentiation phase
(A) STRUCTURES OF THE TRLIMANIR DISC
(i) Endothelial cells
Mesoderm (mesenchymal cells)
o VEGF causes the cells to proliferate and differentiate
→ some areas start specializing and forming tubes
lined by angioblast
Angioblast will give rise to endothelial cells:
o Endothelium
 Lining the blood vessels
Figure 1. The structures of trilaminar disc o Endocardium
Cross section through the embryo around the third week  Line heart cavity
which shows the trilaminar disc composing of:
(ii) Formed elements
(1) Ectoderm
Some mesoderm form hemocytoblast cells inside the
Dorsal part tube which move through the tube
Amniotic cavity above it → this will develop into RBC, WBC and platelets
(2) Mesoderm (formed elements) → move through blood vessels and
heart
Parts of the mesoderm
(3) Canalization
(i) Paraxial mesoderm Tubes formed will connect (canalize between one
Which separates into blocks of cells called somites another) → make one long tube → blood vessel with
formed elements moving inside of it
(ii) Intermediate mesoderm
(C) ANGIOGENESIS
Develops into the gonads & urinary system
Blood vessels made sprout more blood vessels
(iii) Lateral plate mesoderm
Structures of the lateral plate mesoderm include: Remember:
o Intraembryonic coelom in between the two plates Vasculogenesis
o Somatic layer of lateral plate o Mesoderm developed into blood vessels
 Moves with the ectoderm and around the Angiogenesis
amniotic cavity o Blood vessels made from blood vessels
o Splanchnic layer of lateral plate
 Involves in development of cardiovascular
system
 Moves with the endoderm and around the yolk
sac
(3) Endoderm
Gives way to the gut tube: Figure 2. Vasculogenesis vs angiogenesis
o Foregut
o Midgut
o Hindgut
o Pharyngeal apparatus
Ventral part
Yolk sac below it
(4) Neural tube
In between the mesoderm
(5) Notochord
Below the neural tube
DEVELOPMENT OF VASCULAR SYSTEM EMBRYOLOGY: Note #1. 1 of 7

II) THE HEART TUBE III) CROSS SECTION OF EMBRYO
Endoderm release VEGF → lateral mesoderm At the level of aortic sac

proliferates and differentiates forming Will show structures including the:
o 2 heart tubes/blood vessels at the front o Developing arterial system
 undergo folding process → fusion of the 2 tubes o Aortic sac
o 2 dorsal aortae behind the heart tube o Dorsal aortae
 Undergo folding → fusion o Ectoderm
o Endoderm which will develop into gut tube
(A) LATERAL PLATE FOLDING  Foregut
Folding causes all the layers to come together and  Midgut
make cylindrical shape  Hindgut
o Heart tubes become 1 which also gives the blood  Primitive pharynx with the pharyngeal apparatus
vessels • The highest part of the gut tube
o Dorsal aorta comes off the heart tube and move o Neural tube
backwards into 2 dorsal aortae → fuse together as it o Notochord
moves down the embryo
Figure 5. Embryonic cut section
(A) PHARYNGEAL ARCH

Structures of the upper part of pharyngeal arch include:
o Pharyngeal pouches
 The inner part
o The arches
Figure 3. Lateral plate folding  Mesoderm around the pharyngeal pouches
(B) PARTS OF HEART TUBE o Clefts/grooves
 Ectoderm forming the outer part of the pharyngeal
From the below upwards: arch
o Sinus venosus with the inflow tracts, drain the
 Cardinal veins
 Umbilical veins
 Vitelline veins
o Primitive atria
o Primitive ventricle
o Bulbus cordis Figure 6. Structures of pharyngeal arch
o Truncus arteriosus
o Aortic sac which moves backwards into the dorsal
aortae
Figure 4. The heart tube and its structures
2 of 7 EMBRYOLOGY: Note #1. DEVELOPMENT OF VASCULAR SYSTEM

(B) AORTIC ARCH
(i) Angiogenesis
Blood vessels bridging to the dorsal aorta
o Aortic sac makes blood vessels which reach the
pharyngeal arches
o Pharyngeal arches which are mesoderm make blood
vessels reaching to the dorsal aorta
This is formed at multiple levels → making a total of 6
aortic arches
The 5th doesn’t form or if it does, it regresses quickly
(ii) Arteries developed from the arches:

st
1 aortic arch
o Maxillary artery
2nd aortic arch
(C) MAJOR BLOOD VESSELS
o Hyoid artery → will developed into stapedial artery
(very rare to exist in humans, only 10%)
3rd aortic arch
o Common carotid arteries, and proximal part of
internal carotid arteries
4th aortic arch
o The right arch will form the right subclavian artery
and parts of brachiocephalic artery
o The left arch will form the aortic arch after the
brachiocephalic artery
 Which is from the left common carotid until the
left subclavian
• Subclavian arteries supply the arms Figure 8. The major blood vessels
• Aortic arch continues downwards into (i) Pulmonary trunk
descending aorta → abdomen reaching the
common iliac arteries → external iliac arteries From truncus arteriosus → splits into pulmonary
supplying the lower limbs arteries
o Right pulmonary artery
6th aortic arch
o Left pulmonary artery
o The right arch will form the right pulmonary artery
o Left arch will form the left pulmonary artery and Between pulmonary trunk and aorta is the ductus
ductus arteriosus arteriosus of the embryo
(ii) Ascending aorta

From truncus arteriosus
(iii) Aortic arch

From the left fourth arch
o Give branch to left and right subclavian and
common carotid arteries
o Goes down to descending aorta → abdomen → lower
limb
Figure 7. The aortic arch

IV) SYSTEMIC CIRCULATION
(A) DESCENDING AORTA

The dorsal aortae fuse downwards and supply lower
(2) Progression to an adult circulation
parts of the embryo
The general branches will develop to form the adult
circulation
(i) Dorsolateral branches

Intercostal and lumbar arteries
(ii) Lateral branches

Adrenal/suprarenal arteries supplying the adrenal
glands
o Adrenal sits on the kidneys
Renal arteries → supplying the kidneys
Gonadal arteries supplying the gonads
o Developing embryo have gonads → these later
become ovaries or testicles
(iii) Vitelline artery

Vitelline artery which goes to the yolk sac breaks into 3
Figure 9. Descending aorta of a fetus parts to supply the gut tube
o Celiac artery → supplying the foregut
(1) Beginning of fetal circulation o Superior mesenteric artery → supplying the midgut
Descending aorta goes down the length of embryo and o Inferior mesenteric artery → supplying the hindgut
gives of 4 general branches
o Dorsolateral branches (iv) Common iliac arteries
 From the back Split into internal and external iliac arteries
o Lateral branches o In the internal → have internal iliac arteries
 From the sides  Umbilical arteries descend and come off the
o Vitelline artery internal iliac arteries (Figure 10) → becomes the
 From the center adult remnant of umbilical artery which is the
 Runs into the yolk sac through the vitellin duct medial umbilical ligament
 The vitelline duct connects the embryo to the yolk o Umbilical part that persists → forms the superior
sac vesical artery → supplies the bladder
o Right and left umbilical arteries o External iliac arteries → supply lower limbs
 At the beginning point of branching of the dorsal
aorta
Figure 10. Descending aorta of a fecal development

approaching adult circulation. Note the development of iliac
arteries

V) VENOUS CIRCULATION (B) VITELLINE SYSTEM
Remember: (1) Embryonic life

Parts of the heart tube from the below upwards: Vitelline system consists of the right and left veins
o Sinus venosus with the inflow tracts, drain the These form plexus around the GI tract (the right and left,
 Cardinal veins respectively)
 Umbilical veins → move to the liver to give off capillaries called
 Vitelline veins sinusoids (very permeable)
o Primitive atria The blood from the sinusoids drains into hepatic veins
o Primitive ventricle → moves pass the septum transversum (future
o Bulbus cordis diaphragm)
o Truncus arteriosus → to reach sinus venosus
o Aortic sac which moves backwards into the dorsal o This is the right and left hepatocardiac channel
aortae
(A) SINUS VENOSUS Remember:

o Vitelline system connects the yolk sac to the heart
(2) Development to adult life
(i) Left vitelline vein digression

The left vitelline system will start to digress
The right vitelline system will dominate
o More blood goes to the right vein, which then
enlarges in size → capillaries network formed,
taking blood from the spleen and gastrointestinal tract
Figure 11. Cut section of sinus venosus → draining it into the liver feeding both sinusoids
Cut section of the sinus venosus and the inflow tracts  Splenic veins
(Figure 11) will show: • From the spleen
 Superior mesenteric vein
(1) The right side • Upper part of the gut
Right horn gives rise to  Inferior mesenteric vein
o Right posterior cardinal vein • Lower part of gut tube
 Drain blood from the bottom The hepatic portal vein, which combines all the three
o Right anterior cardinal vein veins above → drains the blood into the sinusoids of the
 Drain blood from the top liver
o Right common cardinal vein
 Connecting the two cardinal veins (ii) Hepatic veins formation
→ blood will empty into the right horn → which When the left vitelline vein digresses, the right
empties into the sinus venosus hepatocardiac channel receives blood from the left and
(2) The left side right sinusoids
o This forms the right and left hepatic veins
Left horn gives rise to:
o Left post cardinal vein (iii) Inferior vena cava formation
 from the bottom
When the two hepatic veins combine together → it will
o Left anterior cardinal vein
become the inferior vena cava → this empty into the
 from the top
right horn → sinus venosus → primitive atria which
o Left common cardinal vein
becomes the right atrium
 Connecting the two cardinal veins → blood will
empty into the left horn → which empties into the
sinus venosus
(3) The middle
Umbilical veins
o Medial to the right and left horns respectively
Vitelline system (right and left vitelline veins)
o The most medial portion
Remember:
The right side is dominant in the venous system
o The left sided veins will either shift their supply to the
right side or degenerate

(C) UMBILICUS SYSTEM LOWER PART OF VENOUS CIRCULATION
(1) Embryonic life After the degeneration of the posterior cardinal veins,
Placenta gives off right and left umbilical veins three systems will develop
o The right vein will digress From the top to the bottom:
o Supracardinal veins
(i) Ductus venosus o Subcardinal veins
Left umbilical vein reaches the bottom portion of o Sacro-cardinal veins
inferior vena cava, near the liver → this is called the These will drain blood from abdominal cavity and lower
ductus venosus limbs
o It also gives branches to the liver along the way
(1) Supracardinal veins
It is the bridging vein between the left umbilical vein and
the inferior vena cava (i) Intercostal veins
o Ductus venosus have a lot of smooth muscle
Supracardinal veins have branches:
 This enables it to control the blood flow that
o Branches of left supracardinal veins
comes into the circulation
 4,5,6,7
 All the blood that flows to the heart via the
 Which forms the left intercostal veins
umbilical venous circulation, need to go
o Branches of the right supracardinal veins
through ductus venosus before draining into
 4,5,6,7,8,9,10,11
inferior vena cava
 Which form the right intercostal vein
(2) Adult:
(ii) Azygos and hemiazygos
(i) Ligamentum teres Anastomosis happen between the left and right
When the yolk sac degenerate → the whole system supracardinal veins
regress, cutting the umbilical cord o The blood will primarily flow from left to the right
The umbilical vein will become ligamentum teres which draining the respective intercostals → empty into
is an adult remnant that connects around the liver superior vena cava
The right supracardinal vein will become the azygos
(ii) Ligamentum venosum vein
Ductus venosus → becomes fibrotic adult remnant → The left supracardinal vein which shunts the blood to
ligamentum venosum the right will become the hemiazygos
(D) CARDINAL SYSTEM

(2) Subcardinal veins
Remember:
On both sides, left and right: Right and left subcardinal vein have three branches
o Anterior cardinal vein and the posterior cardinal vein which drains the following organs on both sides
connect → forming common cardinal vein which respectively
drains into right/left horn respectively → into sinus o Adrenal glands
venosus o Kidneys
o Gonads
UPPER PART OF VENOUS CIRCULATION
(i) Renal portion of inferior vena cava
(i) Digression of posterior cardinal vein The left subcardinal vein → degenerates
Left anterior cardinal vein → forms shunt connection at The blood from the left side drains into the right
the top to the right anterior cardinal veins subcardinal vein → this forms the renal portion of the
Anything above the shunt will remain intact inferior vena cava
o This drains the head The renal portion of inferior vena cava drains the right
and left adrenal glands, kidneys and gonads
Anything below the shunt → digress
o The blood then drains into the inferior vena cava →
(ii) Superior vena cava right atrium
Right common cardinal vein below the level of (3) Sacro-cardinal veins
anastomosis becomes the superior vena cava In the embryonic life, the sacro-cardinal veins drain the
(iii) Brachiocephalic veins blood from the lower limbs separately (right and left side)
The right anterior cardinal vein at the level and above (i) Lumbosacral portion of the inferior vena cava
the shunt/anastomosis will become the right Development into the adult life, the blood from the left
brachiocephalic vein sacro-cardinal vein will shift to right
The shunt/anastomosis which is form the left side is o Left sacro-cardinal vein will degenerate, at the
now the left brachiocephalic vein portion just above the drainage of the lower limb →
(iv) Internal jugular and subclavian veins shunt into right sacro-cardinal vein
o Right sacro-cardinal which is now the lumbosacral
On the right side, the right brachiocephalic vein is portion of the inferior vena cava receives blood
formed by the confluence of the right subclavian and from the right and left lower limb
internal jugular veins
On the left side, above the shunt (left brachiocephalic
vein) → the left internal jugular and subclavian veins
also drains into the brachiocephalic vein

(E) SUMMARY VI) REVIEW QUESTIONS
Hepatic inferior vena cava is derived from the right
1) Which mesodermal layer gives rise to the
vitelline vein
endocardial heart tubes?
Renal portion of inferior vena cava is derived right
a) Paraxial mesoderm
subcardinal vein
b) Somatic mesoderm
Sacral portion/post renal portion of inferior vena cava is
c) Intermediate mesoderm
derived from the right sacro-cardinal vein
d) Splanchnic mesoderm
2) Which heart chamber does the right horn of the
sinus venosus contribute to during development of
the fetal heart?
a) Left atrium
b) Right atrium
c) Right ventricle
d) Common ventricle
3) Which part of the primitive heart tube gives rise to
the pulmonary artery and the aorta?
a) Bulbus cordis
b) Primitive atrium
c) Primitive ventricle
d) Sinus venosus
e) Truncus arteriosus
4) During vascular development, the hepatic portal
venous system arises from:
a) umbilical veins
b) vitelline veins
c) subcardinal veins
d) supracardinal veins
5) The supracardinal veins give rise to
a) Azygos veins
b) Common iliac veins
c) Hepatic veins
d) Suprarenal veins
6) The right brachiocephalic vein is formed from the

a) Supracardinal vein
b) Right common cardinal vein
c) Right anterior cardinal vein
d) Left anterior cardinal vein
7) Regarding ligamentum teres, which is true?
a) It is the adult remnant of ductus venosus
b) It is the bridging vein of left umbilical to inferior vena
cava
c) It is the adult remnant of umbilical vein
d) The persistence into adult life causes death
8) Regarding aortic arch, which is false?
a) There are a total of 6 arches formed
b) 1st arch give rise to mandibular artery
c) 5th arch regresses quickly
d) 4th arch give rise to subclavian artery
9) All of the following are structures forming the heart
tube except
a) Primitive atria
b) Primitive ventricle
c) Bulbus cortical
d) Truncus arteriosus
Figure 12. The venous system
10) Regarding inferior vena cava, which is true?
a) It is the combination of two hepatic portal veins
b) It is the combination of two portal veins
c) It empties into the left horn
d) It is formed from the umbilical system
CHECK YOUR ANSWERS
VII) REFERENCES
Sadler TW. Langman's Medical Embryology. Philadelphia: Wolters Kluwer; 2019.
Le T. First Aid for the USMLE Step 1 2020. 30th anniversary edition: McGraw Hill; 2020.
Marieb EN, Hoehn K. Anatomy & Physiology. Hoboken, NJ: Pearson; 2020.
Boron WF, Boulpaep EL. Medical Physiology.; 2017.

ECTODERM
Ectoderm Medical Editor: Jan Camille M. Santico
OUTLINE II) NEURULATION

I) GASTRULATION ● The cells from the primitive node continue to migrate
II) NEURULATION cranially, forming a tube/cord underneath the ectoderm
and in between the mesoderm. This tube is the
III) ECTODERMAL DERIVATIVES notochord.
IV) APPENDIX ● The notochord secretes growth factors and proteins
V) REVIEW QUESTIONS which induces the overlying ectoderm cells to proliferate
and thicken, forming the neural plate
VI) REFERENCES ● The neural plate proliferates and invaginates along its
central axis, forming the neural groove and neural folds
● The neural folds move closer and fuse, forming the
I) GASTRULATION neural tube
o The lateral parts of the neural fold differentiate into
● The inner cell mass of a blastocyst differentiates into a neural crest cells
bilaminar disc, which is made up of: o The neural crest cells detach once the folds fuse
o Epiblast
o Hypoblast ● See Figure 4. Neurulation [Moore et al, 2016]
● Gastrulation is the process wherein the three germ III) ECTODERMAL DERIVATIVES
layers and the axial orientation are established in the
embryo [Moore et al, 2016] (A) NEURAL TUBE DERIVATIVES
o The bilaminar disc is converted into a trilaminar disc ● Anterior neuropore
● Prechordal plate o Cranial end of the neural tube
o thickened portion of the endodermal layer located o Closes around day 24/25 (with sufficient folate
towards the cranial end of the embryo supplementation)
● Primitive Streak ● Posterior neuropore
o A thickened linear band of epiblast located caudally in o Caudal end of the neural tube
the median plane of the dorsal aspect of the o Closes around day 26-28
embryonic disc [Moore et al, 2016] ● Failure of these neuropores to close will result in spina
o See Figure 3. Gastrulation [Moore et al, 2016] bifida, anencephaly, myelomeningocele, etc
● Primitive node ● The neural tube undergoes vesiculation to form the
o An enlarged group of cells located in the anterior central nervous system
portion of the primitive streak o Neurons
● At the primitive node, some epiblast cells invaginate and o Glial cells (astrocytes, oligodendrocytes)
migrate downwards and towards the cranial end, forming o Posterior pituitary
a third layer in between the epiblast and hypoblast. o Pineal gland
● The migrating epiblast cells in between the epiblast and o Retina
hypoblast form the mesoderm (B) NEURAL CREST CELL DERIVATIVES
● The migrating epiblast cells invade the hypoblast layer
below, converting it into endoderm ● Mnemonic: CREST CELL
● The epiblast layer on top differentiates into ectoderm o Chromaffin cells (adrenal medulla)
o Rostral tissues (connective tissue, bones, and
muscles of the head and neck)
o Enteric nervous system
o Satellite cells and Schwann cells (glial cells of PNS)
o The PNS (spinal nerves, ganglia)
o Carotid bodies (measure concentrations of oxygen
and CO2)
o Endocardial cushions (forming the septum and valves
of the heart)
o Light skin/dark skin – melanocytes
o Leptomeninges of the brain (pia mater, arachnoid
mater)
Figure 1. Gastrulation
ECTODERM EMBRYOLOGY: Note #1. 1 of 4

(C) PLACODES (D) SURFACE ECTODERM
● All the remaining parts of the embryonic surface not
covered by the placode and the neural plate are
considered surface ectoderm
● Surface ectoderm differentiates into epithelial tissue
o Epidermis
o Nails
o Hair
o Sweat glands
o Lining of nasal cavity (except roof, comes rom
olfactory placode)
o Lining of oral cavity
o External ear canal
o Lining of inferior anus (below pectinate line)
Figure 2. Placodes ● Rathke’s pouch
o Invagination/budding of epithelial tissue along the
● Ectodermal placodes are thickened areas of the cranial nasal pharynx
ectoderm which differentiate into various structures o Differentiates into the anterior pituitary gland
o Fuses with the posterior pituitary gland precursor
(1) Olfactory placode (from the hypothalamus) to form the pituitary gland
● Differentiates into olfactory epithelium
o Tissue at the roof of the nasal cavity Remember
o Includes the receptor cells and supporting cells Mnemonic for Ectodermal Derivatives: ECTODERM
o Function: smell Epithelial tissue (inside and outside the body)
Central nervous system
(2) Lens placode The lens placode
Otic and Olfactory placode
● Differentiates into the lens Dang neural crest cells
o Function: far/near vision; allows the eye to focus on Eyes (retina)
objects at varying distances Rathke’s pouch  anterior pituitary gland
o Ciliary muscles control the lens, turning it globular or Melatonin (from pineal gland)
flat to adjust the focusing power
(3) Otic placode
● Differentiates into the inner ear, which is made up of:
o Cochlea – hearing, sound waves
o Vestibule – static equilibrium
o Semicircular canals – dynamic equilibrium
(4) Precursors of Cranial Nerve Ganglia
● Nodose placode  nodose ganglia
● Trigeminal placode  trigeminal ganglia
● Geniculate placode  geniculate ganglia
2 of 4 EMBRYOLOGY: Note #1. ECTODERM

IV) APPENDIX
Figure 3. Gastrulation [Moore et al, 2016]
Figure 4. Neurulation [Moore et al, 2016]
ECTODERM EMBRYOLOGY: Note #1. 3 of 4

V) REVIEW QUESTIONS
What is the thickened linear band of epiblast cells

which is vital to gastrulation?
a. Prechordal plate
b. Primitive node
c. Primitive groove
d. Primitive streak
Which structure induces the formation of the neural

plate?
a. Primitive streak
b. Prechordal plate
c. Notochord
d. Rathke’s pouch
Which of the following is NOT a derivative of the

neural tube?
a. Retina
b. Posterior pituitary gland
c. Lens
d. Pineal gland
Which of the following is NOT a neural crest cell

derivative?
a. Chromaffin cells
b. Nodose ganglion
c. Spinal nerves
d. Melanocytes
surface ectoderm?
a. Hair
b. Sweat glands
c. Lining of the oral cavity
d. Lining of the duodenum
CHECK YOUR ANSWERS
VI) REFERENCES
● Moore, K.; Persaud, T.V.N. & Torchia, M. (2016). The
Developing Human: Clinically Oriented Embryology. 10th Ed.
Elsevier
4 of 4 EMBRYOLOGY: Note #1. ECTODERM

1. ENDODERM
Endoderm Medical Editor: Jan Camille M. Santico
OUTLINE
I) EMBRYONIC DEVELOPMENT
II) ENDODERMAL DERIVATIVES
IV) REFRENCES
I) EMBRYONIC DEVELOPMENT
(A) GASTRULATION & NOTOCHORD FORMATION (B) EMBRYONIC FOLDING
Recall: Gastrulation is the process wherein the three (1) Lateral Folding
germ layers and the axial orientation are established in
the embryo [Moore et al, 2016] Lateral folding produces right and left lateral folds which
o The bilaminar disc is transformed into a trilaminar disc fuse to form a cylindrical embryo
Can be visualized through a cross-section of the embryo
The primitive streak and primitive node develop, through o Better for visualizing the gut cavities and sections of
which epiblast cells migrate. the gut tube
The migration of epiblast cells through the primitive streak
forms three new layers:
o Endoderm – epiblast cells invade the hypoblast layer
o Mesoderm – epiblast cells form a new layer in
between the epiblast and hypoblast
o Ectoderm – epiblast cells differentiate into this
Epiblast cells also migrate through the primitive node,
extending cranially to form the notochord.
Figure 1. Lateral Folding [Sadler, 2019]
(2) Longitudinal Folding / Cranio-caudal Folding

Longitudinal folding produces the head and tail folds
Can be visualized through a sagittal section of the
embryo
o Better for:
 visualizing the entire length of the gut tube
 Distinguishing the sections of the gut (foregut,
midgut, hindgut)
 understanding the derivations of the endoderm
o This view shows the connection between the gut and
the yolk sac
Figure 2. Longitudinal Folding [Sadler, 2019]
(C) FUSED MEMBRANES

Buccopharyngeal membrane
o An area of ectoderm directly fused to the endoderm in
the cranial end of the embryo
o Will break down to become the mouth
Cloacal membrane
o An area of ectoderm directly fused to the endoderm in
the caudal end of the embryo
o Will break down to become the anus
ENDODERM EMBRYOLOGY: Note #1. 1 of 3

II) ENDODERMAL DERIVATIVES Table 1. Derivatives of Pharyngeal Pouches
Pharyngeal
The endoderm forms the epithelial lining of the gut tube Derivative
Pouch
The gut tube is divided into three sections/parts: Middle Ear/Tympanic Cavity
o Foregut 1st
Auditory Tube/Eustachian Tube
o Midgut
Tonsils (tubal, pharyngeal, lingual,
o Hindgut 2nd
palatine)
Superior parathyroid gland
rd th Inferior parathyroid gland
3 and 4
Parafollicular cells (C cells)
Thymus gland
Figure 3. Formation of the Primitive Gut [Sadler, 2019]
(A) FOREGUT DERIVATIVES

Pharynx Figure 4. Pharyngeal Apparatus [Sadler, 2019]
Esophagus
Stomach (E) FUSED MEMBRANES
First two parts of the duodenum
(1) Buccopharyngeal membrane
GIT-associated Organs
o Respiratory bud/diverticulum  respiratory tract Fused ectoderm and endoderm in the cranial region of
o Hepatic  liver, gallbladder, head of pancreas the embryo
o Pancreatic  body and tail of pancreas Will form the mouth
(2) Cloacal Membrane
(B) MIDGUT DERIVATIVES Fused ectoderm and endoderm in the caudal region of
Last two parts of the duodenum the embryo
Jejunum Will form the urethra and anal canal
Ileum The cloaca will bifurcate:
Cecum o One part moves anteriorly to form the urogenital
Ascending colon sinus, which forms the following:
Proximal 2/3 of the transverse colon  bladder
 urethra
(C) HINDGUT DERIVATIVES  prostate gland (in males)
Distal 1/3 of transverse colon o One part moves posteriorly to form the anal canal
Descending colon  The pectinate line separates the endoderm and
Sigmoid colon ectoderm derived portions of the anal canal
Rectum • Superior 2/3 of anal canal – endoderm
Anal canal • Inferior 1/3 – ectoderm
(D) PHARYNX
The primitive pharynx is derived from endoderm
o A bud from the primitive pharynx forms the thyroid
The pharyngeal apparatus is also derived from
endoderm. It consists of:
o Pharyngeal arches
o Pharyngeal pouches
o Pharyngeal grooves
o Pharyngeal membranes
The inner membranes of the pharyngeal apparatus are Figure 5. Bifurcation of the Cloacal Membrane [Sadler, 2019]
lined by endoderm
Remember
Mnemonic for Endodermal Derivatives: ENDO
Epithelial lining of GIT (pharynx to first 2/3 of anal canal)
Neck (thyroid, thymus, parathyroid glands)
Drainer (bladder, urethra)
Organs associated with GIT (lungs, liver, pancreas)
2 of 3 EMBRYOLOGY: Note #1. ENDODERM

Which of the following organs is NOT an

endodermal derivative?
a. Liver
b. Pancreas
c. Spleen
d. Stomach
Which of the following is a derivative of the midgut?

a. First two parts of the duodenum
b. Proximal 2/3 of the transverse colon
c. Sigmoid colon
d. Rectum
The tonsils are derived from which pharyngeal

arch?
a. 1st
b. 2nd
c. 3rd
d. 4th
The cloacal membrane forms which of the following

structures?
a. Urethra and anal canal
b. Ureter and urethra
c. Rectum and anal canal
d. Vas deferens and urethra
Which of the following is NOT a foregut derivative?

a. Pharynx
b. Esophagus
c. Stomach
d. Jejunum
CHECK YOUR ANSWERS
IV) REFRENCES
Elsevier
● Sadler,T.W. (2019). Langman’s Medical Embryology. 14th Ed.
Wolters Kluwer
ENDODERM EMBRYOLOGY: Note #1. 3 of 3

FERTILIZATION, CLEAVAGE, BLASTULATION

Fertilization, Cleavage, Blastulation Medical Editor: Jan Camille M. Santico
OUTLINE II) FERTILIZATION

I) OVULATION
● After sperm is ejaculated into the female reproductive
II) FERTILIZATION
tract, it travels through the uterus until it meets the
III) CLEAVAGE
secondary oocyte at the ampulla
IV) BLASTULATION
● Sperms undergo a period of capacitation, wherein a
V) REVIEW QUESTIONS
glycoprotein coat and seminal proteins are removed from
VI) REFERENCES
the surface of the sperm acrosome [Moore et al, 2016]
● The sperm then binds to the ZP3 (zona pellucida)
I) OVULATION
receptor on the oocyte membrane
(A) ANATOMY OF THE UTERUS o Recall: The zona pellucida is an extracellular coat
surrounding oocytes
● This binding triggers the release of lytic enzymes from the
acrosome, which allows the sperm to penetrate the zona
pellucida
● The plasma or cell membranes of the oocyte and sperm
fuse, allowing the sperm to release its nuclei into the
oocyte cytoplasm.
● The sperm nuclei (23 chromosomes) and the oocyte
nuclei (23 chromosomes) will fuse, forming a diploid cell
(46 chromosomes) called the zygote
Additional Information [Moore et al, 2016]

● Fertilization
o Stimulates the penetrated oocyte to complete the second
meiotic division
o Restores the normal diploid number of chromosomes
Figure 1. Anatomy of the Uterus [medlineplus.gov] (46) in the zygote
● The parts of the uterus include: o Results in variations of the human species through
o Vagina mingling of maternal and paternal chromosomes
o Cervix o Determines the chromosomal sex of the embryo
o Body of the uterus o Causes metabolic activation of the ootid (nearly mature
o Fundus of the uterus oocyte) and initiates cleavage of the zygote
o Fallopian tubes
o Ampulla of the fallopian tube
 Dilated region; site of fertilization
III) CLEAVAGE
o Fimbriae
 Finger-like structures which sweep the oocyte into ● Cleavage consists of repeated mitotic divisions of the
the fallopian tube zygote, resulting in a rapid increase in the number of cells
[Moore et al, 2016]
(B) OVULATION CYCLE o At this stage, each cell is called a blastomere
● On day 14/15 of the ovulation cycle, the body starts o Occurs as the zygote passes along the uterine tube
releasing luteinizing hormone (LH) towards the uterus
● The release of luteinizing hormone from the anterior o Zygote is still within the zona pellucida
pituitary gland is stimulated/triggered by the following: ● The zygote undergoes repeated division, passing through
o Gonadotropin releasing hormone (GnRH) these stages:
 A neuropeptide secreted by the hypothalamus o 2-cell stage
o Estrogen (via positive feedback mechanism) o 4-cell stage
● The surge in luteinizing hormone triggers ovulation by: o 8-cell stage
o Stimulating the ovary to produce large amounts of o 16-cell stage
fluid  pressurizes the Graafian follicle ● When there are 16 or more blastomeres, the zygote is
o Causing prostaglandin release  dilate blood vessels considered a morula (a hollow ball of cells)
 increases capillary leakiness around the Graafian
follicle
o Activates metalloproteinases  breaks down the
connective tissue in the follicle  follicular rupture 
oocyte release
● After ovulation, the oocyte is considered a secondary
oocyte, arrested at meiosis II, metaphase
o The secondary oocyte needs to be fertilized in order
to complete meiosis II
● The finger-like fimbriae “sweep” the secondary oocyte
into the infundibulum of the uterus, then it passes into the
ampulla [Moore et al, 2016]
FERTILIZATION, CLEAVAGE, BLASTULATION EMBRYOLOGY: Note #1. 1 of 2

IV) BLASTULATION V) REVIEW QUESTIONS
● Compaction The hypothalamus releases which hormone to

o The blastomeres change shape and tightly align stimulate the secretion of LH?
themselves against each other to form a compact ball a. CRH
of cells b. GHRH
● Blastulation c. GnRH
o The process wherein the morula is transformed into a d. TRH
blastula/blastocyst
 A group of cells compact around the The secondary oocyte is arrested at which stage of
edge/periphery  will form the outer cell mass meiosis II after ovulation?
 Another group of cells group together on one side a. prophase
 will form the inner cell mass b. metaphase
o A blastula/blastocyst is a ball of cells with an outer cell c. anaphase
mass, inner cell mass, and a hollow, fluid-filled cavity d. telophase
● As the cells become more functional, they differentiate The sperm initially binds to which receptor on the
o Outer cell mass  Trophoblast oocyte membrane?
o Inner cell mass  Embryoblast a. ZP3 receptor
● The trophoblast differentiates into two specialized layers b. Acrosomal receptor
that are important for the placenta: c. Corona radiata receptor
o Cytotrophoblast d. Zygote receptor
● The embryoblast will differentiate into a bilaminar disk, What is the term referring to the cells of a zygote at
which is made up of: the 8-cell stage?
o Epiblast a. Morula
o Hypoblast b. Blastula
c. Blastocyst
d. Blastomere
Which of the following did NOT come from the inner

cell mass?
a. Trophoblast
b. Embryoblast
c. Epiblast
d. Hypoblast
CHECK YOUR ANSWERS
VI) REFERENCES
Elsevier
Figure 2. Cleavage and Blastulation [Moore et al, 2016]
Remember
● The blastula/blastocyst has two parts: outer cell mass and
inner cell mass
o Outer cell mass  Trophoblast
o Inner cell mass  Embryoblast
● The trophoblast will further differentiate into:
o Cytotrophoblast
● The embryoblast will differentiate into a bilaminar disk,
which is made up of:
o Epiblast
o Hypoblast
2 of 2 EMBRYOLOGY: Note #1. FERTILIZATION, CLEAVAGE, BLASTULATION

1. GASTRULATION
Gastrulation Medical Editor: Dr. Sarah Abimhamed
OUTLINE
I) RECALL FROM WEEK 1

II) IMPLANATATION OF THE BLASTOCYST
III) BILAMINAR DISC
IV) DERIVATIVES OF EACH LAYER OF THE
TRILAMINAR DISC:
V) REVIEW QUESTIONS
VI) REFERENCES
I) RECALL FROM WEEK 1

Prior to this, watch:
o Fertilization
o Fertilization, Cleavage, Blastulation
To learn about development up until week 1.
QUICK OVERVIEW
After Fertilization:
Figure 2. Cleavage of Cells After Fertilization
The anterior pituitary releases LH to trigger the ovulation
process. II) IMPLANATATION OF THE BLASTOCYST
o Secondary oocyte is formed When the cell is implanted in the endometrium, cells start
o It is frozen in metaphase II. proliferating outside the zona pellucida
o In the ampulla, fertilization occurs The cell membrane will disintegrate.
o Cleavage process occurs, the cell transforms: It forms a fluid-like cytoplasm which consists of the nuclei
Oocyte → Zygote → 4-cell stage → 8-cell stage of the cell. Therefore, the cells lose their well-defined
→ 16-cell stage → Blastocyst margins
Components of the cell will be released and all of the
As these processes are occurring, the cells are moving to cytoplasm will fuse together to form a syncytium
the uterine cavity at the same time.  This is called the syncytiotrophoblast
At the base of the finger-like structures of the
Proteins in the blastocyst allow it to hook up onto the syncytiotrophoblast there are well-defined margins.
endometrium to implant itself.  This is called the cytotrophoblast
Syncytiotrophoblast will continue to release hydrolytic

enzymes to make its way through the uterine lining.
The uterine lining has maternal blood vessels and the
syncytiotrophoblast will move deeper into the
endometrium until it becomes confluent with the maternal
blood vessels
o Now the embryo can receive oxygen, nutrients,
hormones, etc.
At day 24, the syncytiotrophoblast starts making β-hCG

It stimulates the corpus luteum to continue producing
Figure 1. Fertilization and Ovulation progesterone
o This helps avoid the endometrial lining from shedding
Structure of Trophoblast:
like in the normal cell cycles.
The outer cell is the trophoblast, it will become:
o Cytotrophoblast
The inner cell mass differentiated and became more
specialized to form the bilaminar disc
Trophoblast forms:
o Part of chorion
o Part of placenta
This helps in providing oxygen and nutrients and get rid of
waste. Figure 3. Implantation of the Cell in the Uterus, showing the
structure of Trophoblast
Gastrulation EMBRYOLOGY: Note #1. 1 of 3

III) BILAMINAR DISC Epiblast cells will move through the primitive groove, and
where the hypoblast is and replace it to form the
This is the inner cell mass of the differentiated blastocyst. endoderm.
It contains 2 sheet like layers (the top and bottom layer) At this stage the epiblast layer is called ectoderm.
(1) Top layer
Called the Epiblast
o Above the epiblast is the amniotic cavity.
(2) Bottom layer

Called the Hypoblast
o Below the hypoblast is the yolk sac.
Figure 6. Formation of Primitive Groove and Primitive Pit as
well as process that enables epithelial migration
Formation of the mesoderm & ectoderm:
After the endoderm is formed, more FGF-8 is released
causing more epiblast cells to migrate and move through
the primitive groove.
Then they move cranially and fill up the area between the
epiblast layer and the hypoblast, this is called the
Figure 4. Bilaminar Disc Showing Epiblast and Hypoblast mesoderm.
Now the bilaminar disc is transformed to a trilaminar disc.

(3) From the top view o This process is called gastrulation.
On one end of the bilaminar disc (from the top view), Formation of the Notochord
there is a depression → prochordal plate
o This is an area where the epiblast and hypoblast are More FGF-8 is released, ectodermal cells continue to
fused together. migrate, unlike previously where the cells migrated
o The prochordal plate helps to give orientation. through the primitive groove, now they are migrating
 As it is located in the cranial side, opposite to the cranially through the primitive pit towards the prochordal
prochordal plate is the caudal side. plate.
This forms a tube called the notochord, that moves
On the caudal side, there is a membrane called the
underneath the ectoderm but above the endoderm (can
cloacal membrane
be seen through the sagittal view)
o Becomes the anus
o Note there is no mesoderm here.
On the cranial side, there is buccopharyngeal
membrane Areas where there is no mesoderm:
o Becomes the mouth
o Near the notochord
o Prochordal Plate
o Cloacal Plate
Table 1. Structures before and after differentiation

Before After
Cytotrophoblast
Trophoblast
Figure 5. Bilaminar Disc from the top view
Syncytiotrophoblast
Primitive streak Primtive groove
DIFFERENTIATION OF THE BILAMINAR DISC Primitive node Primitive pit
At week 2 – week 3 Epiblast Ectoderm
Hypoblast Endoderm
Formation of the primitive groove and primitive pit: Notochord Neural tube
Epiblast cells begin to thicken → forms primitive streak. Bilaminar disc Trilaminar disc
At the end of the streak, the primitive node is formed
(towards the cranial end) Significance of the notochord:
o Induces neuralation (neural tube formation)
Eventually, some cells in the center of the primitive streak o In the annulus fibroses of the vertebral disc, there is a
and primitive node start dying. This forms a cavity called jelly like material called the nucleus pulposus. This
the primitive groove and primitive pit. is an adult remnant of the notochord.
Some cells in the edge of the primitive groove start

secreting chemicals laterally (e.g. Fibroblast Growth
Factor-8)
Formation of the endoderm:
FGF-8 binds on epiblast cells, and triggers an intracellular
process. This activates the protein SNAIL-1.
o SNAIL-1 inhibits the formation of e-cadherins.
 Note: e-cadherins allow cells to stick together
o Inhibition of e-cadherins allows the epiblast cells to Figure 7. Gastrulation Process
move freely for epithelial migration
2 of 3 EMBRYOLOGY: Note #1. Gastrulation

IV) DERIVATIVES OF EACH LAYER OF THE TRILAMINAR DISC:
Other videos go into more details on this.
(A) ECTODERM
(B) MESODERM
o Skin
Differentiates into 3 parts.
o Nervous system
Paraxial part forms:
o Axial skeleton
Intermediate part forms:

o Kidneys
o Gonads
Lateral part forms:

o Splanchnic part (for GI organs)
o Somatic part
(C) ENDODERM
o Lining of GI tract
 Accessory organs
 Glands
V) REVIEW QUESTIONS
1) What are the finger-like processes that helps with
implantation of the blastocyst in the endometrium?
a) Trophoplast
b) Cytotrophoblast
c) Syncytiotrophoblast
d) Zona Pellucida
2) What does the hypoblast turn into at week 2-3?
a) Epiblast
b) Endoderm
c) Ectoderm
d) Primitive node
3) In which position is the cloacal membrane found?

a) Cranial
b) Caudal
c) Dorsal
d) Ventral
4) Which protein inhibit e-cadherins to prevent epiblast

cell adherence?
a) SNAIL-1
b) FGF-8
c) β-hCG
d) FGF-3
5) Which process describes gastrulation?
a) When the epiblast cells migrate to the primitive
groove
b) When the epiblast cells replace the hypoblast to
form the endoderm
c) When the bilaminar disc transforms to a trilaminar
disc
d) When primitive streak starts to form and grow
cranially
CHECK YOUR ANSWERS
VI) REFERENCES
Gastrulation EMBRYOLOGY: Note #1. 3 of 3

1. MESODERM
Mesoderm Medical Editor: Jan Camille M. Santico
In the second week, the primitive streak and primitive

OUTLINE node develop
o FGF8 is released, causing epiblast cells to migrate
I) EMBRYONIC DEVELOPMENT through the primitive streak
II) MESODERMAL DERIVATIVES  Move downward, laterally, and cranially (towards
the prechordal plate)
IV) REFRENCES
o The migration of epiblast cells forms three new layers:
I) EMBRYONIC DEVELOPMENT  Endoderm – epiblast cells invade the hypoblast
layer
Recall: Gastrulation is the process wherein the three  Mesoderm – epiblast cells form a new layer in
germ layers and the axial orientation are established in between the epiblast and hypoblast
the embryo [Moore et al, 2016]  Ectoderm – epiblast cells differentiate into this
o The bilaminar disc is transformed into a trilaminar disc o Epiblast cells also migrate through the primitive node
The inner cell mass of a blastocyst differentiates into two  Move downward and cranially, forming a tubular
layers: process called the notochord
o Epiblast – on top of this is the amniotic sac  The notochord is found below the ectoderm and in
o Hypoblast – below this is the yolk sac between the mesoderm
The notochord secretes proteins and growth factors (GH
and SHH) to:
o induce the overlying ectoderm to undergo the
neurulation process
o trigger the adjacent mesoderm to differentiate
II) MESODERMAL DERIVATIVES

The mesoderm differentiates into:
o Paraxial mesoderm (most medial) (A) PARAXIAL MESODERM
o Intermediate mesoderm The paraxial mesoderm is the most medially located
o Lateral plate mesoderm (most lateral) portion of the mesoderm
 Somatic layer / Somatopleure It segments into chunks called somites
 Splanchnic layer / Splanchnopleure Each somite develops a cavity in the center called a
somitocoele, which extends and separates the somite
into two halves:
o Dermatomyotome  dermatome + myotome
o Sclerotome
(1) Dermatome
The dermatome forms the following structures:
o Spinal meninges
o Skin (dermis and subcutaneous tissue)
(2) Myotome
The myotome forms the following structures:
Figure 1. Mesodermal Differentiation at 18 days [Moore, 2016] o Muscle tissue
o Epaxial muscles (dorsal muscles of the back)
o Hypaxial muscles (trunk and limb muscles)
(3) Sclerotome
The sclerotome forms the following structures:
o Vertebrae (body, spinous process, vertebral process)
o Intervertebral discs
o Ribs
Figure 2. Mesodermal Differentiation at 21 days [Moore, 2016]
Figure 3. Somite Differentiation [Gilbert, 2000]
MESODERM EMBRYOLOGY: Note #1. 1 of 3

(B) INTERMEDIATE MESODERM (2) Somatic Layer / Somatopleure / Parietal Mesoderm
The intermediate mesoderm is located in between the Located beneath the ectoderm
paraxial mesoderm and lateral mesoderm Differentiates into:
It forms the following structures: o Parietal pleura
o Renal system o Pericardium
 Kidneys o Peritoneum
 Ureters o Sternum (parts)
o Gonads o Limb buds
 Male: testes  Lateral plate mesoderm then moves into the limb
 Female: ovaries buds to create the bones and cartilage
o Ductal System
(3) Splanchnic Layer / Splanchnopleure / Visceral
 Male: epididymis, vas deferens
Mesoderm
 Female: fallopian tubes, uterus
Located near the endoderm
(C) LATERAL PLATE MESODERM Differentiates into:
(1) Folding of Embryo [Moore et al, 2016] o Visceral pleura
o Visceral pericardium
The embryo undergoes folding in the median and o Visceral peritoneum
horizontal planes due to rapid growth. o Adrenal cortex
This transforms the embryo from a trilaminar disc into a o Spleen
cylindrical embryo. o Smooth muscle of the GIT (visceral layer)
Folding in the median plane produces head and tail folds, o Development of cardiovascular system
which can be visualized in sagittal section (See Figure 4. o Development of structures made by red bone marrow
Folding in the Median Plane )  Myeloid stem cells (neutrophils, basophils,
Folding in the horizontal plane produces right and left eosinophils)
lateral folds, which fuse at the median plane to form a  Lymphoid stem cells
cylindrical embryo  Erythroid stem cells
o Can be visualized in cross section (See Figure 5.
Folding in the Horizontal Plane ) Remember
o This folding makes the following structures more Mnemonic for Mesodermal Derivatives: MESODERMAL CELLS
apparent: Myeloid stem cells
 Intraembryonic coelom Erythroid stem cells
 Somatopleure / Somatic mesoderm Spleen
 Splanchnopleure / Splanchnic mesoderm gOnads
Dermis
Entire trunk
Renal system
Meninges
Adrenal cortex
Lymphoid stem cells / Lymph nodes
Cardiovascular system
Endothelium of blood vessels
Lining of body cavities (visceral and parietal)
Limbs
Smooth muscle of GIT
Figure 4. Folding in the Median Plane [Sadler, 2019]
Figure 5. Folding in the Horizontal Plane [Sadler, 2019]
2 of 3 EMBRYOLOGY: Note #1. MESODERM

Which of the following is a derivative of paraxial

mesoderm?
a. Kidney
b. Basophil
c. Dermis
d. Spleen

sclerotome?
a. Vertebral body
b. Ribs
c. Radius
d. Intervertebral discs
The parietal pleura is derived from which type of

mesoderm?
a. Paraxial mesoderm
b. Intermediate mesoderm
c. Somatic mesoderm
d. Splanchnic mesoderm

intermediate mesoderm?
a. Kidneys
b. Testes
c. Fallopian Tubes
d. Adrenal cortex
Which of the following is a derivative of the

splanchnopleure?
a. Adrenal cortex
b. Parietal peritoneum
c. Subcutaneous tissue
d. Spinal meninges
CHECK YOUR ANSWERS
IV) REFRENCES
● Gilbert SF. Developmental Biology. 6th edition. Sunderland
(MA): Sinauer Associates; 2000. Paraxial Mesoderm: The Somites
and Their Derivatives.
Elsevier
● Sadler,T.W. (2019). Langman’s Medical Embryology. 14th Ed.
Wolters Kluwer
MESODERM EMBRYOLOGY: Note #1. 3 of 3

8. NEURULATION, VESICULATION, NEURAL CREST CELL MIGRATION

Embryology | Neurulation, Vesiculation, Neural Crest Cell Migration Medical Editor: Gerard Jude Loyola
OUTLINE
By day 18, as the edges of the neural plate move toward
I) NEURULATION one another, it forms the neural folds and the neural
II) VESICULATION groove
III) NEURAL CREST CELL DIFFERENTIATION o Neural groove: U-shaped canal formed by the
IV) FORMATION OF THE SPINAL CORD involution of the neural plate
V) SUPPLEMENTARY IMAGES Cells around the edges of the neural folds specialize and
VI) REVIEW QUESTIONS
differentiate to become neural crest cells
VII) REFERENCES
o Important for the development of different structures
in the peripheral nervous system
I) NEURULATION
(C) NEURAL TUBE FORMATION
Process in which the neural plate involute to form the
neural tube By day 21, edges of the neural fold fuse with one another
→ neural groove completely involutes → forming the
neural tube
Recall (refer to Figure 1):
o Neural tube comes underneath the ectoderm (Figure
The trilaminar disc contains:
2)
o Ectoderm (blue)
o Mesoderm (red) o Neural crest cells (orange) are found by the neural
o Endoderm (blue green) tube
o Notochord is found below the neural tube
The mesodermal-derived cells move through the
o Ectoderm is found above the neural tube
primitive pit forming the notochord
Anterior and posterior neuropores are still open (Figure 3)
(A) NEURAL PLATE FORMATION o As cells continue to proliferate, these neuropore close
o Folate (3-5 mg/d) is important in closing the
neuropores so the cells are able to synthesize DNA
and replicate
Figure 1. Neurulation showing the formation of the neural plate.
• Notochord releases growth factors (e.g. fibroblast, TGF-

β)
• By day 17, ectodermal cells start to proliferate (called
ectodermal proliferation) → forming the neural plate
• As the neural plate thickens, the embryo allows the Figure 3. Dorsal view of the neural tube showing an open
neural plate to involute neuropores. *Correction: neuropore instead of neutopole.
o The center of the neural plate pulls down and the
edges roll toward one another
(1) Clinical Significance
(B) NEURAL FOLDS AND NEURAL GROOVE
FORMATION Lack of folate → neuropores remain open → neural tube
defects
o Anencephaly and encephalocele (when the anterior
neuropore failed to close)
o Spina bifida cystica or occulta (when the posterior
neuropore failed to close)
Complications with spina bifida:
o Arnold-Chiari (Type II) malformation
 Cerebellar tissue and brainstem herniate through
the foramen magnum, often accompanied by
occipital encephalocele and lumbar
myelomeningocele [Moore et al, 2016]
o Dandy Walker syndrome
o Tethered cord syndrome
Complications with encephalocele
Figure 2. (Top) Formation of the neural folds, neural groove
and the neural crest cells by day 18. (Bottom) Complete o Meckel Gruber syndrome
involution of the neural folds forming the neural tube.
NEURULATION, VESICULATION, NEURAL CREST CELL MIGRATION EMBRYOLOGY: Note #1. 1 of 5

 Presents with cystic renal dysplasia, polydactyly, II) VESICULATION
and protrusion of the brain and meningeal tissues
to the occipital area
Neural tube defects are among the most common
congenital anomalies [Moore et al, 2016]
o Primary disturbance, such as teratogenic drugs,
affects cell fates, cell adhesion and mechanism
of neuropore closure resulting in failure of the
neural folds to close and form the neural tube
Figure 6. Vesiculation of the neural tube.
Spina bifida occulta
o Neural tube defect resulting from failure of the Process of forming the brain, brainstem and the spinal
halves of one or more neural arches to fuse in cord from the neural tube
the median plane [Moore et al, 2016]
(A) PRIMARY VESICLES
Spina bifida cystica
o Neural tube defect involving protrusion of the
spinal cord and/or meninges through defects in
the vertebral arches [Moore et al, 2016]
Figure 7. Three primary vesicles from the neural tube.

Neural tube forms the three primary vesicles
Figure 4. (A) Spina bifida occulta; (B-D) Spina bifida o Prosencephalon
cystica [Moore et al, 2016]. o Mesencephalon
o Rhombencephalon
The brain begins to develop during the third week, when
(2) Closure of the Neuropores
the neural plate and tube develop from the
neuroectoderm [Moore et al, 2016]
(B) SECONDARY VESICLES
Figure 5. Closure of the anterior and posterior neuropores.

By day 24, anterior neuropore closes followed by the Figure 8. Secondary vesicles.
closure of the posterior neuropore by day 26
The complete closure of the neural tube leads to the The primary vesicles proliferate and differentiate to more
development of the central nervous system secondary vesicles:
o Prosencephalon differentiates to:
 Telencephalon
Neural tube differentiates into the CNS [Moore et al, 2016]
Neural crest gives rise to cells that form the ANS • “Looks like a telescope”
and PNS [Moore et al, 2016]  Diencephalon
o Mesencephalon
Table 1. Summary of neurulation. o Rhombencephalon differentiates to:
Day Remarks  Metencephalon
 Myencephalon
15-17 Notochord formation
o The remaining of the neural tube becomes the spinal
Ectodermal proliferation cord
17
Formation of neural plate The secondary vesicles are formed during the fifth week
Formation of the neural groove and neural [Moore et al, 2016]
18
folds
Complete involution of the neural groove
21 forming the neural tube
Anterior and posterior neuropores still intact
24 Closure of the anterior neuropore
26 Closure of the posterior neuropore
2 of 5 EMBRYOLOGY: Note #8. NEURULATION, VESICULATION, NEURAL CREST CELL MIGRATION

(C) FORMATION OF THE CNS o Important for catecholamine surge for stress response
o Recall: Preganglionic axons synapse in the
postganglionic motor neuron → release epinephrine
and norepinephrine
Submucosal (Meissner’s) plexus and myenteric
(Auerbach’s) plexus
o Important in the enteric nervous system
o Found within the submucosa and muscularis externa
of the GIT
o Helps regulate the gastrointestinal tract
Dorsal root ganglion
o Pseudounipolar cells located outside the spinal cord
Collateral and chain ganglia
o Preganglionic sympathetic fiber in the lateral gray
horn (T1-L2) project to the chain (paravertebral) or
Figure 9. Primary structures of the CNS formed from the collateral (prevertebral) ganglia
secondary vesicles. Leptomeninges
The secondary vesicles then form the structures of the o Arachnoid + pia mater
CNS: o Surround the brain and spinal cord
o Telencephalon differentiates to: The dura mater is derived from the mesoderm [Ghannam
 Cerebral hemispheres & Al Kharazi, 2021].
o Diencephalon differentiates to: Cranial nerves V, VII, IX and X
 Thalamus, subthalamus, hypothalamus, o Innervates the pharyngeal arches
epithalamus, pineal gland and mammillary bodies o Some sources/books also include CN III and VIII
o Mesencephalon differentiates to: Head and neck
 Midbrain o Neural crest cells also differentiate to different
o Metencephalon becomes the structures of the head and neck
 Pons and cerebellum  Muscles and bones (e.g. malleus, stapes and
o Myelencephalon becomes the incus)
 Medulla
o Spinal cord IV) FORMATION OF THE SPINAL CORD
Table 2. Summary of the differentiation of the primary vesicle,

secondary vesicle to the primary CNS structures.
CNS
Primary Secondary
Structure
Telencephalon Cerebrum
Thalamus
Hypothalamus
(including the Figure 11. Cross-section of the caudal neural tube.
Prosencephalon mammillary The neural tube has three layers (Figure 11):
Diencephalon bodies)
o Marginal zone
Subthalamus
Epithalamus  Outermost layer
(including the  Where neurons and axons start forming
pineal gland) o Mantle zone
 Middle layer
Mesencephalon Mesencephalon Midbrain
 Where neuroblasts are found
Pons o Neuroepithelial zone
Metencephalon
Rhombencephalon Cerebellum  Innermost layer
Myelencephalon Medulla
Cells from the neuroepithelial cells proliferate to become
neuroblasts and eventually, they develop to neurons and
move outward the neural tube
III) NEURAL CREST CELL DIFFERENTIATION
(A) ALAR PLATE AND BASAL PLATE
As cells differentiate and move away from the neural
tube, they make the alar and basal plate
(1) Alar Plate
“Bunny ears” extending dorsally and laterally
Differentiates to become the posterior gray horn (PGH)
o Where sensory neurons are found
Figure 10. Overview of neural crest cell differentiation.
(2) Basal Plate
Neural crest cells migrate and differentiate to different Anterior and lateral extension of the neural tube
structures Differentiates to become the ventral gray horn (VGH)
Melanocytes o Where motor neurons are found
o Found in the skin (3) Neural Tube Remnants
o Produce skin pigments
Enterochromaffin cells in the adrenal medulla Remnants of the neural tube becomes the spinal canal
o Secrete epinephrine (80%) and norepinephrine (20%) containing CSF

V) SUPPLEMENTARY IMAGES
Figure 12. The neural plate folds to form the neural tube. A, Dorsal view shows an embryo of approximately 17 days that was exposed by
removing the amnion. B, Transverse section of the embryo shows the neural plate and early development of the neural groove and neural
folds. C, Dorsal view of an embryo of approximately 22 days shows that the neural folds have fused opposite the fourth to sixth somites
but are spread apart at both ends. D to F, Transverse sections of the embryo at the levels shown in C illustrate formation of the neural
tube and its detachment from the surface ectoderm. Some neuroectodermal cells are not included in the neural tube crest [Moore et al, 2016].
Figure 13. Schematic illustration shows the embryologic basis of neural tube defects. Meroencephaly (partial absence of brain) results
from defective closure, and meningomyelocele results from defective closure of the caudal neuropore [Moore et al, 2016].
4 of 5 EMBRYOLOGY: Note #8. NEURULATION, VESICULATION, NEURAL CREST CELL MIGRATION

Figure 14. Diagrammatic sketches of the brain vesicles indicate the adult derivatives of their walls and cavities. The rostral part of the
third ventricle forms from the cavity of the telencephalon. Most of this ventricle is derived from the cavity of the diencephalon [Moore et al, 2016].
VI) REVIEW QUESTIONS

All of the following are derived from the neural crest
cells EXCEPT:
a. Ossicles
b. Dura mater
c. Arachnoid mater
d. Submucosal plexus
All of the following differentiate from the

diencephalon EXCEPT:
a. Temporal lobe
b. Pineal gland
c. Mammillary bodies
d. Thalamus
The sensory neurons from the posterior gray horn is

derived from what structure?
a. Basal plate
b. Alar plate
c. All of the above
d. None of the above
The following statements are TRUE except:

a. Ectodermal cells start to proliferate by day 17.
b. The neural folds and neural groove form by day 18.
c. The neural groove completely involutes to form the
neural tube by day 21.
d. The anterior neuropore closes after the posterior
neuropore, which fuses by day 24.
The following statements are FALSE except:

a. The mantle zone of the neural tube is the middle
layer where neurons and axons start forming.
b. The alar plate is the ventral and lateral extension of
the neural tube.
c. There are five secondary vesicles formed from the
prosencephalon, mesencephalon and
rhombencephalon.
d. Two mg folic acid should be taken by pregnant
women daily to prevent neural tube defects.
CHECK YOUR ANSWERS
VII) REFERENCES
● Moore, K., Persaud, T., & Torchia, M. (2016). The Developing
Human: Clinically Oriented Embryology. Philadelphia: Elsevier.

1. FERTILIZATION
Reproductive System | Fertilization Medical Editor: Donna Stewart
OUTLINE
(5) Fimbriae
I) MAIN HEADING IN ● Finger-like projects located at the ovary side of the

II) CONTENT FORMATTING fallopian tubes. The movement of the projections at
III) APPENDIX ovulation assist in directing the ovum to the fallopian
IV) REVIEW QUESTIONS tube.
V) REFRENCES (6) Ovary
● there are two ovaries, one of each located at the lateral
end of each fallopian tube within the abdominal cavity.
I) FEMALE REPRODUCTIVE SYSTEM Each ovary contains numerous primary follicles. As a
result of hormone production during the menstrual cycle,
a few follicles will mature, with a mature Graafian follicle
releasing an ovum during ovulation. After the release of
the ovum, the remainder of the Graafian Follicle, reseals
and becomes a young corpus luteum, releasing
progesterone, in preparation for a potential fertilization
event to occur.
II) STAGES OF OOCYTE DEVELOPMENT
(A) OOGONIA
this first stage occurs within the fetus of the developing
female, primordial germ cells division to multiply to form
numerous small oogonia.
(1) Primary Oocytes
● at the fifth month of pregnancy of the forming female
fetus, the oogonia undergo the first stage of meiotic
division to form oocytes. Meiotic division will then cease,
until the female fetus, is born and reaches puberty. Upon
reaching puberty, in each menstrual cycle, a few oocyte
follicles will develop, one of these cells will develop into
Graafian follicle to release an ova during ovulation. Note:
Figure 1.1 The female reproductive system only a fraction of the primary Oocytes survives to puberty,
and even fewer will be released over the lifespan of the
(1) Vagina
female reproductive years.
● the lower part of the female reproductive tract: a
muscular tube, lined with mucous membrane, connecting (2) Graafian follicle
the cervix of the uterus to the exterior. It receives semen ● mature follicle containing the primary oocyte which is
that is ejaculated into the upper part of the vagina and released during ovulation. The first meiotic division is
from there the sperms must pass through the cervix and completed producing a secondary oocyte and first polar
uterus to fertilize an ovum in the Fallopian tube. body.
(2) Cervix (B) SECONDARY OOCYTE
● the lower third of the Uterus, being a small neck shaped ● final stage of first meiotic division, where a viable oocyte
connective canal which links the cavity of the uterus with is produced ready for fertilization, with a lesser polar body
the vagina. The canal is lined with mucous membrane being an unusable portion of meiotic division products.
and normally contains mucus, the viscosity of which
changes throughout the menstrual cycle. The cells are (C) DEFINITIVE OVUM
stratified columnar epithelium. ● (mature ovum) production of final female haploid cell,
with 23 chromosomes ready for combination with the
(3) Uterus
male haploid cell and recombinant reproduction.
● (womb) a pear-shaped organ that is about 3 inches
(7.5cm). Suspended in the pelvic cavity by peritoneal (D) POLAR BODY
folds (ligaments) and fibrous bands. The upper two thirds ● small cells of unusable meiotic division products. Polar
are connected to the fallopian tubes, whilst the lower third body products can be produced at the end of the first
being the Cervix projects into the vagina. meiotic division, and additionally at the end of the second
meiotic division. These bodies will be reabsorbed
(4) Fallopian tubes
products.
● a pair of tubes that conduct ova from the ovaries to the
uterus. The ovarian end opens into the abdominal cavity III) FEMALE HORMONES UTILIZED IN FERTILIZATION
with a funnel shaped structure with fine finger-like
projections called Fimbriae. (1) Estrogen
● usually produced from day 1 to 14 of the female
reproductive cycle, it causes some of the uterine glands
Fertilization EMBRYOLOGY: Note #1. 1 of 4

to produce uterine fluid and cervical fluids which cause reproductive system, plus the burrowing function within
capacitation of the sperm cell in phase one of fertilization. the acrosomal reaction. Within the microtubules are two
motility proteins being dynein, a motor protein, and
(2) Lysosome (stored within the oocyte)
tubulin a rail or cytoskeleton protein, which is used to
● will fuse with the cell membrane during fertilization, to move the flagella.
release hydrolytic enzymes to breakdown the zona ● Note: with consumption of excessive alcohol, deficiency
pellucida and its proteins, which hardens the cell of selenium, or exposure to various pesticides, lead or
membrane. radiation can cause mutations of sperm such as multi
headed sperm.
IV) SEMINAL FLUID UTILIZED IN FERTILIZATION VI) MOVEMENT OF SPERM WITHIN THE FEMALE
REPRODUCTIVE SYSTEM
● Seminal fluid is the transport mechanism for sperm and
provides a number of chemicals and nutrients required (A) POST EJACULATION
for fertilization to occur.
● Vesiculase will cause vaginal and seminal fluid to
(1) Seminal vesicles coagulate, and sperm cells adhesion to the sides of the
vagina.
● make up between 60-70% of seminal fluid. Some
important chemicals released are:
o Fructose (carbohydrate fuel source for sperm cell) (B) DURING COAGULASE ADHESION
o Prostaglandins (to contract uterus in retropulsion)
● Fibrinolysins break up some of the coagulation, for sperm
o Coagulase (Vesiculase coagulates vesicular and
cells entry into the cervix and through the female
vaginal fluid for sperm to latch on)
reproductive tracts.
(2) The prostate gland
● makes up the remaining 30-40% of seminal fluid. Some (C) WITHIN THE UTERUS
important chemicals released are:
● Prostaglandins act on the smooth muscle of the uterus,
o Citrate (ketoacid intermediate fuel source)
causing retropulsion of the uterus squeezing the sperm
o Fibrinolysin (breaks up coagulation for sperm cells to
cells further along the reproductive tract.
enter the female reproductive system)
● Seminal plasmin will destroy bacterial cells and microbes
o PSA -Prostate Specific Antigen (used to indicate
in the female genital tract, therefore act like an antibiotic
Benign Prostatic Hyperplasia)
chemical to ensure the reproductive tract is a relatively
o Seminal plasmin (antibiotic to destroy bacterial cells
sterile environment for the stages of reproduction to
and microbes in the female reproductive tract)
occur.
o Seminal relaxin (speeds up motility of sperm through
- Seminal relaxin and the alkaline environment of
the female reproductive tract)
the uterus increase the motility of the sperm,
V) STRUCTURE OF SPERM CELL allowing the sperm to move at a faster rate
through the fallopian tube towards the ampulla
region.
VII) STAGES OF REPRODUCTION
(1) Head
● this portion of the sperm cell contains the nucleus,
which is the 23-chromosome male haploid. There is also
the acrosome which contains an extensive amount of
proteolytic, hydrolytic, and glycolytic enzymes, such as
acrosin.
(2) Mid Piece
● this portion of the sperm cell contains a lot of
mitochondria formed in coils. The mitochondria use the
fructose to produce ATP to power the movement of the
flagella.
(3) Flagella
● this portion of the sperm is arranged in a 9+2
arrangement, where there are nine paired segments of
microtubules formed in a circular formation around the (A) CAPACITATION
outer region of the flagella, and a further two microtubule
● The head of the sperm has numerous products such as
segments located in the middle of the flagella. This
glycoprotein, proteins and cholesterol which cover its
arrangement allows for the powerful movement of the
surface. Capacitation occurs all the way through the
flagella which allows movement of the flagella along the
2 of 4 EMBRYOLOGY: Note #1. Fertilization

female reproductive tract, where the uterine and cervical the Oocyte. This flow of Sodium ions into the cell causes
fluids remove most products from the surface of the head a positive charge across the surface of the cell
of the sperm leaving specific modified glycoproteins as it membrane. The positive charge prevents further sperm
moves toward the zona pellucida for fertilization. cells from binding with the cell membrane. Additionally,
Through capacitation of the sperm, it will become hyper the bound sperm will then further bind to the alpha
motile, allowing it to move quickly through the numerous subunit on the cell membrane causing the head of the
chemicals such as hyaluronic acid which are produced sperm to fuse with the cell membrane and nucleus of the
and released by granulosa cells and move toward the sperm, the male gamete, containing the male haploid (23
Zona Pellucida type 3 receptors (ZP3) upon the Zona chromosome) cell to enter the oocyte.
Pellucida.
(D) SLOW BLOCK TO POLYSPERMY
(B) ACROSOMAL REACTION ● Once the male gamete enters the oocyte, calcium ions
● Once the sperm binds with the ZP3 receptor, Calcium will be released out of the smooth endoplasmic reticulum
ions enter the sperm head. At that stage the membrane into the cell. The calcium causes lysosomal enzymes in
of the sperm head will open, and the vesicle of the the oocyte to bind with the cell membrane and release
acrosome fuses with the receptor. The chemicals hydrolytic enzymes, which break down the Zona
present in the acrosome such are acrosin and proteases Pellucida and all its products. This hardens the cell
are released and start burrowing a hole into the zona membrane, so no further sperm can gain access to the
pellucida, allowing access to the cell membrane of the Oocyte. The calcium ions also cause the secondary
oocyte. oocyte, which is in metaphase II, to finish meiosis II. As
such the oocyte will produce a haploid definitive ovum
(C) FAST BLOCK TO POLYSPERMY and a polar body.
● Once a singular sperm obtains access to the cell
membrane, it will bind with the Beta subunit (and (E) FERTILIZATION
eventually Alpha) on the cell membrane. By binding with ● The Definitive ovum and the male gamete will fuse, and a
the Beta subunit, channels will open through the cell zygote will be formed.
membrane. These channels allow Sodium to flow into
VIII) APPENDIX
d) cervix
IX) REVIEW QUESTIONS 2) The head of the sperm prior to capacitation has what
products attached to it?
1) What location in the female reproductive tract does
a) Cholesterol, proteins, glycoproteins
fertilization take place?
b) Specific modified glycoproteins
a) vagina
c) 9+2 microtubule segments
b) ovary
d) Zona Pellucida
c) fallopian tube
Fertilization EMBRYOLOGY: Note #1. 3 of 4

3) In the acrosomal reaction which receptors do sperm Use style “Ref”
bind to?
a) PSA (example)
b) ZP3 ● APA citation guide. (2016). http://www.bibme.org/citation-
guide/apa/
c) Haploid receptors ● Lipson, C. (2011). Cite right: A quick guide to citation styles
d) Graafian follicle receptors MLA, APA, Chicago, the sciences, professions, and more (2nd ed).
4) At the fifth month of pregnancy of the forming female United States of America: The University of Chicago Press, Ltd.,
London.
fetus, the oogonia undergo the first stage of meiotic ● Ferraro, A. (Photographer). (2014). Liberty enlightening the
division to form oocytes? world [digital image]. Retrieved from
True / False https://www.flickr.com/photos/afer92/ 14278571753/in/set-
5) Estrogen is normally produced on days 15 to 28 of 72157644617030616
the menstrual cycle?
True / False
X) REFERENCES
4 of 4 EMBRYOLOGY: Note #1. Fertilization

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12. DEVELOPMENT OF THE GIT PART 1

OUTLINE II) EMBRYONIC FOLDING

I) TRILAMINAR DISC (A) SAGITTAL PLANE

Development of the GIT Part 1 EMBRYOLOGY: Note #1. 1 of 3

(i) Primary Retroperitoneal Organs

Figure 4. Intraperitoneal Organs

1) Meckel’s diverticulum results from ____

2) Which structure secretes the extraembryonic

3) All of the following structures are intraperitoneal,

4) Which of the following statements is TRUE?

5) Which of the following is NOT a primary

CHECK YOUR ANSWERS

Development of the GIT Part 1 EMBRYOLOGY: Note #1. 3 of 3

13. DEVELOPMENT & EMBRYOLOGY OF THE GI TRACT P2

(2) Definitions (i) The ventral mesogastrium

(ii) The dorsal mesogastrium

(iii) The ventral mesogastrium

Development & Embryology of the GI Tract P2 EMBRYOLOGY: Note #1. 1 of 3

Gastroduodenal a. Upper Superior rectal

2 of 3 EMBRYOLOGY: Note #13. Development & Embryology of the GI Tract P2

1) The following is derived from the ventral

CHECK YOUR ANSWERS

Figure 4. Summary of Vascular Supply and Mesenteries

Development & Embryology of the GI Tract P2 EMBRYOLOGY: Note #1. 3 of 3

17. DEVELOPMENT OF FETAL CIRCULATION

II) BEFORE BIRTH

(A) CONDITION OF LUNGS

(B) HYPOXIC VASOCONSTRICTION

Transmission of maternal antibodies

DEVELOPMENT OF FETAL CIRCULATION EMBRYOLOGY: Note #1. 1 of 8

Sphincter Mechanism of Ductus Venosus

Figure 3. Structure of Umbilical Cord Figure 5. Openings in Right Atrium

(i) Ductus Venosus

(b) SVC (Superior Vena Cava)

Figure 4. Umbilical Vein &

2 of 8 EMBRYOLOGY: Note #17. DEVELOPMENT OF FETAL CIRCULATION

Figure 7. Formation of Umbilical Arteries

(8) Pathway from Right Ventricle

Blood flows from

Right side of heart: HIGH pressure

Left side of heart: LOW pressure

HENCE , MAJORITY OF B LOOD FROM

HENCE , MAJORITY OF B LOOD FROM

DEVELOPMENT OF FETAL CIRCULATION EMBRYOLOGY: Note #1. 3 of 8

Structures that shunt blood AWAY from

III) AFTER BIRTH

(A) EVENTS RIGHT AFTER BIRTH

(B) CHANGES AFTER BIRTH

This is called the FUNCTIONAL closure of Foramen

o Because of this, pressure on Right side of

OPPOSITE pressure gradient to that

Functional- Immediately after birth

Left side > Right side

Figure 12. Pulmonary Circulation

4 of 8 EMBRYOLOGY: Note #17. DEVELOPMENT OF FETAL CIRCULATION

 This means blood is deoxygenated

Blood from lower extremities: Iliac Veins → IVC

(5) Pulmonary Circulation