Wnt Signaling Gradients Establish Planar Cell Polarity by Inducing Vangl2 Phosphorylation Through Ror2

Dev Cell. 2011 Feb 15;20(2):163-76. doi: 10.1016/j.devcel.2011.01.001.

Abstract

It is fundamentally important that signaling gradients provide positional information to govern morphogenesis of multicellular organisms. Morphogen gradients can generate different cell types in specific spatial order at distinct threshold concentrations. However, it is largely unknown whether and how signaling gradients also control cell polarities by acting as global cues. Here, we show that Wnt signaling gradient provides directional information to a field of cells. Vangl2, a core component in planar cell polarity, forms Wnt-induced receptor complex with Ror2 to sense Wnt dosages. Wnts dose-dependently induce Vangl2 phosphorylation of serine/threonine residues and Vangl2 activities depend on its levels of phosphorylation. In the limb bud, Wnt5a signaling gradient controls limb elongation by establishing PCP in chondrocytes along the proximal-distal axis through regulating Vangl2 phosphorylation. Our studies have provided new insight to Robinow syndrome, Brachydactyly Type B1, and spinal bifida which are caused by mutations in human ROR2, WNT5A, or VANGL.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Cell Polarity*
  • Embryonic Development
  • Fibroblasts / cytology*
  • Fibroblasts / metabolism*
  • Mice
  • Models, Biological
  • Nerve Tissue Proteins / metabolism*
  • Phosphorylation
  • Protein Binding
  • Protein Transport
  • Receptor Tyrosine Kinase-like Orphan Receptors / metabolism*
  • Signal Transduction*
  • Wnt Proteins / antagonists & inhibitors
  • Wnt Proteins / metabolism*
  • Wnt-5a Protein
  • beta Catenin / metabolism

Substances

  • Ltap protein, mouse
  • Nerve Tissue Proteins
  • Wnt Proteins
  • Wnt-5a Protein
  • Wnt5a protein, mouse
  • beta Catenin
  • Receptor Tyrosine Kinase-like Orphan Receptors
  • Ror2 protein, mouse