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Publication : Obligatory role for cooperative signaling by pre-TCR and Notch during thymocyte differentiation.

First Author  Ciofani M Year  2004
Journal  J Immunol Volume  172
Issue  9 Pages  5230-9
PubMed ID  15100261 Mgi Jnum  J:89685
Mgi Id  MGI:3041053 Doi  10.4049/jimmunol.172.9.5230
Citation  Ciofani M, et al. (2004) Obligatory role for cooperative signaling by pre-TCR and Notch during thymocyte differentiation. J Immunol 172(9):5230-9
abstractText  The first checkpoint during T cell development, known as beta selection, requires the successful rearrangement of the TCR-beta gene locus. Notch signaling has been implicated in various stages during T lymphopoiesis. However, it is unclear whether Notch receptor-ligand interactions are necessary during beta selection. Here, we show that pre-TCR signaling concurrent with Notch receptor and Delta-like-1 ligand interactions are required for the survival, proliferation, and differentiation of mouse CD4(-)CD8(-) thymocytes to the CD4(+)CD8(+) stage. Furthermore, we address the minimal signaling requirements underlying beta selection and show a hierarchical positioning of key proximal signaling molecules. Collectively, our results demonstrate an essential role for Notch receptor-ligand interactions in enabling the autonomous signaling capacity of the pre-TCR complex.
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