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Publication : Notch, Id2, and RORγt sequentially orchestrate the fetal development of lymphoid tissue inducer cells.

First Author  Cherrier M Year  2012
Journal  J Exp Med Volume  209
Issue  4 Pages  729-40
PubMed ID  22430492 Mgi Jnum  J:183874
Mgi Id  MGI:5319452 Doi  10.1084/jem.20111594
Citation  Cherrier M, et al. (2012) Notch, Id2, and RORgammat sequentially orchestrate the fetal development of lymphoid tissue inducer cells. J Exp Med 209(4):729-40
abstractText  Lymphoid tissue development is initiated during embryogenesis by the migration of lymphoid tissue inducer (LTi) cells from the fetal liver to the periphery, where they induce the formation of lymph nodes and Peyer's patches. In the fetal liver, a subset of common lymphoid progenitors (CLPs) that expresses the integrin alpha4beta7 gives rise to LTi cells, a process strictly dependent on the expression of the transcriptional repressor Id2 and the nuclear hormone receptor retinoic acid-related orphan receptor gamma t (RORgammat). In this study, we show that Id2 and RORgammat are sequentially up-regulated during LTi cell development, matching two waves of differentiation with opposite requirements for Notch signaling. Both the expression of Id2 and Notch are required for the generation of alpha4beta7(+) RORgammat(-) fetal progenitors, but Notch subsequently blocks progression to the RORgammat(+) stage and final maturation of LTi cells. Notch is therefore a necessary switch to engage the LTi developmental pathway, but needs to be turned off later to avoid diversion to the T cell fate.
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