Publication Date:
2013-07-24
Description:
T-cell development depends upon interactions between thymocytes and thymic epithelial cells (TECs). The engagement of Delta-Like 4 (DL4) on TECs by Notch1 expressed by blood-borne BM-derived precursors is essential for T-cell commitment in the adult thymus. In contrast to the adult the earliest T-cell progenitors in the embryo originate in the fetal liver and migrate to the non-vascularized fetal thymus via chemokine signals. Within the fetal thymus some T-cell precursors undergo programmed TCRγ and TCRδ rearrangement and selection, giving rise to unique γδ T cells. Despite these fundamental differences between fetal and adult T-cell lymphopoiesis we show here that DL4-mediated Notch signaling is essential for the development of both αβ and γδ T-cell lineages in the embryo. Deletion of the DL4 gene in fetal TECs results in an early block in αβ T-cell development and a dramatic reduction of all γδ T-cell subsets in the fetal thymus. In contrast to the adult no dramatic deviation of T-cell precursors to alternative fates was observed in the fetal thymus in the absence of Notch signaling. Taken together our data reveal a common requirement for DL4-mediated Notch signaling in fetal and adult thymopoiesis This article is protected by copyright. All rights reserved
Print ISSN:
0014-2980
Electronic ISSN:
1521-4141
Topics:
Medicine
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