Wnt signaling regulates left-right axis formation in the node of mouse embryos

Dev Biol. 2013 Aug 15;380(2):222-32. doi: 10.1016/j.ydbio.2013.05.011. Epub 2013 May 21.


The node triggers formation of the left-right axis in mouse embryos by establishing local asymmetry of Nodal and Cerl2 expression. We found that Wnt3 is expressed in perinodal crown cells preferentially on the left side. The enhancer responsible for Wnt3 expression was identified and found to be regulated by Foxa2 and Rbpj under the control of Notch signaling. Rbpj binding sites suppress enhancer activity in pit cells of the node, thereby ensuring crown cell-specific expression. In addition, we found that the expression of Gdf1 and Cerl2 is also regulated by Notch signaling, suggesting that such signaling may induce the expression of genes related to left-right asymmetry as a set. Furthermore, Cerl2 expression became symmetric in response to inhibition of Wnt-β-catenin signaling. Our results suggest that Wnt signaling regulates the asymmetry of Cerl2 expression, which likely generates a left-right difference in Nodal activity at the node for further amplification in lateral plate mesoderm.

Keywords: Left–right axis; Mouse embryo; Node; Notch signaling; Wnt.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Patterning*
  • Female
  • Hepatocyte Nuclear Factor 3-beta / physiology
  • Immunoglobulin J Recombination Signal Sequence-Binding Protein / physiology
  • Intercellular Signaling Peptides and Proteins / physiology
  • Mice
  • Mice, Inbred ICR
  • Wnt Signaling Pathway / physiology*
  • Wnt3 Protein / physiology


  • Dte protein, mouse
  • Foxa2 protein, mouse
  • Immunoglobulin J Recombination Signal Sequence-Binding Protein
  • Intercellular Signaling Peptides and Proteins
  • Rbpj protein, mouse
  • Wnt3 Protein
  • Wnt3 protein, mouse
  • Hepatocyte Nuclear Factor 3-beta