Obligatory role for cooperative signaling by pre-TCR and Notch during thymocyte differentiation.
Published
Journal Article
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.
Full Text
Duke Authors
Cited Authors
- Ciofani, M; Schmitt, TM; Ciofani, A; Michie, AM; Cuburu, N; Aublin, A; Maryanski, JL; Zúñiga-Pflücker, JC
Published Date
- May 1, 2004
Published In
Volume / Issue
- 172 / 9
Start / End Page
- 5230 - 5239
PubMed ID
- 15100261
Pubmed Central ID
- 15100261
International Standard Serial Number (ISSN)
- 0022-1767
Digital Object Identifier (DOI)
- 10.4049/jimmunol.172.9.5230
Language
- eng
Conference Location
- United States