Wnt5a-Ror-Dishevelled signaling constitutes a core developmental pathway that controls tissue morphogenesis

Hsin-Yi Henry Ho, Michael W. Susman, Jay B. Bikoff, Yun Kyoung Ryu, Andrea M. Jonas, Linda Hu, Rejji Kuruvilla, Michael Eldon Greenberg

Research output: Contribution to journalArticle

147 Scopus citations

Abstract

Wnts make up a large family of extracellular signaling molecules that play crucial roles in development and disease. A subset of noncanonical Wnts signal independently of the transcription factor β-catenin by a mechanism that regulates key morphogenetic movements during embryogenesis. The best characterized noncanonical Wnt, Wnt5a, has been suggested to signal via a variety of different receptors, including the Ror family of receptor tyrosine kinases, the Ryk receptor tyrosine kinase, and the Frizzled seven-transmembrane receptors. Whether one or several of these receptors mediates the effects of Wnt5a in vivo is not known. Through loss-of-function experiments in mice, we provide conclusive evidence that Ror receptors mediate Wnt5a-dependent processes in vivo and identify Dishevelled phosphorylation as a physiological target of Wnt5a-Ror signaling. The absence of Ror signaling leads to defects that mirror phenotypes observed in Wnt5a null mutant mice, including decreased branching of sympathetic neuron axons and major defects in aspects of embryonic development that are dependent upon morphogenetic movements, such as severe truncation of the caudal axis, the limbs, and facial structures. These findings suggest that Wnt5a-Ror-Dishevelled signaling constitutes a core noncanonical Wnt pathway that is conserved through evolution and is crucial during embryonic development.

Original languageEnglish (US)
Pages (from-to)4044-4051
Number of pages8
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number11
DOIs
StatePublished - Mar 13 2012
Externally publishedYes

Keywords

  • Axon branching
  • Noncanonical wnt signaling
  • Ror1
  • Ror2
  • Tissue elongation

ASJC Scopus subject areas

  • General

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