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.
Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, 1066, Epalinges, Switzerland.
Anita
A
Wolfer
Anne
A
Wilson
Mohamed
M
Nemir
H Robson
HR
MacDonald
Freddy
F
Radtke
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