Mesp2 initiates somite segmentation through the Notch signalling pathway

Nat Genet. 2000 Aug;25(4):390-6. doi: 10.1038/78062.

Abstract

The Notch-signalling pathway is important in establishing metameric pattern during somitogenesis. In mice, the lack of either of two molecules involved in the Notch-signalling pathway, Mesp2 or presenilin-1 (Ps1), results in contrasting phenotypes: caudalized versus rostralized vertebra. Here we adopt a genetic approach to analyse the molecular mechanism underlying the establishment of rostro-caudal polarity in somites. By focusing on the fact that expression of a Notch ligand, Dll1, is important for prefiguring somite identity, we found that Mesp2 initiates establishment of rostro-caudal polarity by controlling two Notch-signalling pathways. Initially, Mesp2 activates a Ps1-independent Notch-signalling cascade to suppress Dll1 expression and specify the rostral half of the somite. Ps1-mediated Notch-signalling is required to induce Dll1 expression in the caudal half of the somite. Therefore, Mesp2- and Ps1-dependent activation of Notch-signalling pathways might differentially regulate Dll1 expression, resulting in the establishment of the rostro-caudal polarity of somites.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Body Patterning / genetics
  • Embryo, Mammalian / metabolism
  • Female
  • Gene Expression Regulation, Developmental
  • Humans
  • Ligands
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mice, Transgenic
  • Mutation
  • Presenilin-1
  • Receptors, Notch
  • Signal Transduction*
  • Somites / physiology*
  • Transcription Factors / genetics
  • Transcription Factors / physiology*

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Ligands
  • Membrane Proteins
  • Mesp2 protein, mouse
  • PSEN1 protein, human
  • Presenilin-1
  • Receptors, Notch
  • Transcription Factors