Journal
DEVELOPMENT
Volume 147, Issue 12, Pages -Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.178988
Keywords
Foxn1; Notch; Lineage; mTEC; Thymus
Categories
Funding
- National Institutes of Health [R21 AI107465]
- Canadian Institutes of Health Research grant [FND-154332]
- Ontario Graduate Scholarship
- Canada Research Chair in Developmental Immunology
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The cortical and medullary thymic epithelial cell (cTEC and mTEC) lineages are essential for inducing T cell lineage commitment, T cell positive selection and the establishment of self-tolerance, but the mechanisms controlling their fetal specification and differentiation are poorly understood. Here, we show that notch signaling is required to specify and expand the mTEC lineage. Notch1 is expressed by and active in TEC progenitors. Deletion of Notch1 in TECs resulted in depletion of mTEC progenitors and dramatic reductions in mTECs during fetal stages, consistent with defects in mTEC specification and progenitor expansion. Conversely, forced notch signaling in all TECs resulted in widespread expression of mTEC progenitor markers and profound defects in TEC differentiation. In addition, lineage-tracing analysis indicated that all mTECs have a history of receiving a notch signal, consistent with notch signaling occurring in mTEC progenitors. These data provide strong evidence fora requirement for notch signaling in specification of the mTEC lineage.
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