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Inactivation of Notch1 impairs VDJbeta rearrangement and allows pre-TCR-independent survival of early alpha beta Lineage Thymocytes.
Notch proteins influence cell fate decisions in many developmental systems. During lymphoid development, Notch1 signaling is essential to direct a bipotent T/B precursor toward the T cell fate, but the role of Notch1 at later stages of T cell development remains controversial. We have recently reported that tissue-specific inactivation of Notch1 in immature (CD44(-) CD25(+)) thymocytes does not affect subsequent T cell development. Here, we demonstrate that loss of Notch1 signaling at an earlier (CD44(+)CD25(+)) developmental stage results in severe perturbation of alpha beta but not gamma delta lineage development. Immature Notch1(-/-) thymocytes show impaired VDJ beta rearrangement and aberrant pre-TCR-independent survival. Collectively, our data demonstrate that Notch1 controls several nonredundant functions necessary for alpha beta lineage development.
Animals, Cell Survival, Gene Rearrangement, beta-Chain T-Cell Antigen Receptor/physiology, Integrases/metabolism, Membrane Proteins/physiology, Mice, Mice, Transgenic, Receptor, Notch1, Receptors, Antigen, T-Cell, alpha-beta/physiology, Receptors, Cell Surface, T-Lymphocytes/physiology, Transcription Factors, Viral Proteins/metabolism
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