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.
Wolfer
Anita
A
Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, 1066, Epalinges, Switzerland.
Wilson
Anne
A
Nemir
Mohamed
M
MacDonald
H Robson
HR
Radtke
Freddy
F
D000818:Animals; D002470:Cell Survival; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor / Q000502:physiology*; D019426:Integrases / Q000378:metabolism; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D051881:Receptor, Notch1; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology*; D011956:Receptors, Cell Surface; D013601:T-Lymphocytes / Q000502:physiology*; D014157:Transcription Factors; D014764:Viral Proteins / Q000378:metabolism
D008565:Membrane Proteins; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011956:Receptors, Cell Surface; D014157:Transcription Factors; D014764:Viral Proteins; C045073:Cre recombinase; D019426:Integrases