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Publication : Wnt signaling gradients establish planar cell polarity by inducing Vangl2 phosphorylation through Ror2.

First Author  Gao B Year  2011
Journal  Dev Cell Volume  20
Issue  2 Pages  163-76
PubMed ID  21316585 Mgi Jnum  J:169766
Mgi Id  MGI:4942219 Doi  10.1016/j.devcel.2011.01.001
Citation  Gao B, et al. (2011) Wnt signaling gradients establish planar cell polarity by inducing Vangl2 phosphorylation through Ror2. Dev Cell 20(2):163-76
abstractText  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.
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