RRC ID 47322
Author Sasaki N, Kiso M, Kitagawa M, Saga Y.
Title The repression of Notch signaling occurs via the destabilization of mastermind-like 1 by Mesp2 and is essential for somitogenesis.
Journal Development
Abstract The rostro-caudal polarity within a somite is primarily determined by the on/off state of Notch signaling, but the mechanism by which Notch is repressed has remained elusive. Here, we present genetic and biochemical evidence that the suppression of Notch signaling is essential for the establishment of rostro-caudal polarity within a somite and that Mesp2 acts as a novel negative regulator of the Notch signaling pathway. We generated a knock-in mouse in which a dominant-negative form of Rbpj is introduced into the Mesp2 locus. Intriguingly, this resulted in an almost complete rescue of the segmental defects in the Mesp2-null mouse. Furthermore, we demonstrate that Mesp2 potently represses Notch signaling by inducing the destabilization of mastermind-like 1, a core regulator of this pathway. Surprisingly, this function of Mesp2 is found to be independent of its function as a transcription factor. Together, these data demonstrate that Mesp2 is a novel component involved in the suppression of Notch target genes.
Volume 138(1)
Pages 55-64
Published 2011-1-1
DOI 10.1242/dev.055533
PII dev.055533
PMID 21098559
MeSH Animals Basic Helix-Loop-Helix Transcription Factors / genetics Basic Helix-Loop-Helix Transcription Factors / metabolism* Blotting, Western Cells, Cultured Female Gene Expression Regulation, Developmental / genetics Gene Expression Regulation, Developmental / physiology Immunohistochemistry Male Mice Mice, Knockout Mice, Mutant Strains Nuclear Proteins / genetics Nuclear Proteins / metabolism* Receptors, Notch / genetics Receptors, Notch / metabolism* Reverse Transcriptase Polymerase Chain Reaction Signal Transduction / genetics Signal Transduction / physiology* Somites / embryology* Transcription Factors / genetics Transcription Factors / metabolism*
IF 5.611
Times Cited 30
WOS Category DEVELOPMENTAL BIOLOGY
Resource
DNA material pCMV-NICD 3xFLAG (RDB14500)