Notch Signaling Plays an Important Role in mTEC Specification during Fetal Thymus Development

Thymic epithelial cells (TECs) are a vital element of the thymic microenvironments that direct T cell differentiation and repertoire selection, and are thus indispensable for development of a functional immune system. TECs are thought to derive from a bipotent thymic epithelial progenitor cell (TEPC) that differentiates into the functionally distinct cortical (c) and medullary (m) TEC sub-lineages. TEC differentiation is orchestrated by the transcription factor FOXN1. However, the precise mechanisms regulating TEC differentiation, and divergence of the cTEC and mTEC sub-lineages is not yet understood. Here, we have used bioinformatics analysis in conjunction with experimental validation to investigate the molecular regulation of the early development and specification of the thymic epithelium. Our data demonstrate an important role for Notch signaling pathway in mTEC specification during fetal thymus development.