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

Language

  • eng

Conference Location

  • United States