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Keywords:

  • Wnt5a;
  • Lrp6;
  • somitogenesis;
  • development

Abstract

Lrp6 is generally described as a receptor required for signal transduction in the Wnt/β-catenin pathway. Wnt5a, however, is a Wnt ligand that usually does not activate Wnt/β-catenin but rather activates noncanonical Wnt signaling. We have previously shown that Lrp6 can inhibit noncanonical Wnt5a/Wnt11 signaling and that Lrp5/6 loss-of-function produces noncanonical gain-of function defects, which can be rescued by loss of Wnt5a. Here, we describe other phenotypes found in Wnt5a/Lrp6 compound mutant mice, including a worsening of individual Wnt5a or Lrp6 loss of function phenotypes. Lrp6 haploinsufficiency in a Wnt5a−/− background caused spina bifida and exacerbated posterior truncation. Wnt5a−/−Lrp6−/− embryos displayed presomitic mesoderm morphogenesis, somitogenesis, and neurogenesis defects, which are much more severe than in either of the single mutants. Interestingly these results reveal a further level of complexity in processes in which Wnt5a and LRP6 cooperate, or oppose each other, during mouse development. Developmental Dynamics 239:237–245, 2010. Published 2009 Wiley-Liss, Inc.