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.
- URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12121668
Keywords: 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 ; Research Support ; Non-U.S. Gov't ; T-Lymphocytes/*physiology ; *Transcription Factors ; Viral Proteins/metabolism
Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, 1066, Epalinges, Switzerland.
Record created on 2006-12-05, modified on 2016-08-08