Transcriptional regulation of thymus organogenesis and thymic epithelial cell differentiation

Transcriptional regulatory networks are the central regulatory mechanisms that control organ identity, patterning, and differentiation. In the case of the thymus, several key transcription factors have been identified that are critical for various aspects of thymus organogenesis and thymic epithelial cell (TEC) differentiation. The thymus forms from the third pharyngeal pouch endoderm during embryogenesis. Organ development progresses from initial thymus cell fate specification, through multiple stages of TEC differentiation and cortical (cTEC) and medullary (mTEC) formation. Transcription factors have been identified for each of these stages: a Hoxa3-dependent cascade at initial fate specification, Foxn1 for early (and later) TEC differentiation, and NF-kappaB for mTEC differentiation. As important as these factors are, their interrelationships are not understood, and many more transcription factors are likely required for complete thymus organogenesis to occur. In this chapter, we review the literature on these known genes, as well as identify gaps in our knowledge for future studies.