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* Department of Immunology, University of Toronto, Sunnybrook and Women’s College Health Sciences Centre, Toronto, Ontario, Canada;
Division of Immunology, Infection and Inflammation, University of Glasgow, Glasgow, United Kingdom; and
Institut National de Science et Recherche Medicale Unité 503, IFR 128 BioSciences Lyon-Gerland, Lyon, France
The first checkpoint during T cell development, known as 
selection, requires the successful rearrangement of the TCR- 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 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 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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