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Publication : The repression of Notch signaling occurs via the destabilization of mastermind-like 1 by Mesp2 and is essential for somitogenesis.

First Author  Sasaki N Year  2011
Journal  Development Volume  138
Issue  1 Pages  55-64
PubMed ID  21098559 Mgi Jnum  J:167045
Mgi Id  MGI:4867098 Doi  10.1242/dev.055533
Citation  Sasaki N, et al. (2011) The repression of Notch signaling occurs via the destabilization of mastermind-like 1 by Mesp2 and is essential for somitogenesis. Development 138(1):55-64
abstractText  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.
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