Wnt-5A/Ror2 Regulate Expression of XPAPC Through an Alternative Noncanonical Signaling Pathway

Dev Cell. 2007 May;12(5):779-92. doi: 10.1016/j.devcel.2007.02.016.

Abstract

XWnt-5A, a member of the nontransforming Wnt-5A class of Wnt ligands, is required for convergent extension movements in Xenopus embryos. XWnt-5A knockdown phenocopies paraxial protocadherin (XPAPC) loss of function: involuted mesodermal cells fail to align mediolaterally, which results in aberrant movements and a selective inhibition of constriction. XWnt-5A depletion was rescued by coinjection of XPAPC RNA, indicating that XWnt-5A acts upstream of XPAPC. XWnt-5A, but not XWnt-11, stimulates XPAPC expression independent of the canonical Wnt/beta-catenin pathway. We show that transcriptional regulation of XPAPC by XWnt-5A requires the receptor tyrosine kinase Ror2. XWnt-5A/Xror2 signal through PI3 kinase and cdc42 to activate the JNK signaling cascade with the transcription factors ATF2 and c-jun. The Wnt-5A/Ror2 pathway represents an alternative, distinct branch of noncanonical Wnt signaling that controls gene expression and is required in the regulation of convergent extension movements in Xenopus gastrulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Cadherins / genetics*
  • Cadherins / metabolism
  • Cell Polarity
  • Cell Shape
  • Embryo, Nonmammalian / cytology
  • Gene Expression Regulation, Developmental*
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Mice
  • Phosphatidylinositol 3-Kinases / metabolism
  • Signal Transduction*
  • Transcription, Genetic
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism*
  • Wnt-5a Protein
  • Xenopus Proteins / genetics
  • Xenopus Proteins / metabolism*
  • Xenopus laevis / embryology*
  • cdc42 GTP-Binding Protein / metabolism

Substances

  • Cadherins
  • Pcdh8 protein, Xenopus
  • Wnt Proteins
  • Wnt-5a Protein
  • Wnt5a protein, Xenopus
  • Xenopus Proteins
  • Phosphatidylinositol 3-Kinases
  • JNK Mitogen-Activated Protein Kinases
  • cdc42 GTP-Binding Protein