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Developmental Cell
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Developmental Cell
Article . 2011
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Wnt Signaling Gradients Establish Planar Cell Polarity by Inducing Vangl2 Phosphorylation through Ror2

Authors: Gao, B; Economides, AN; Elliot, G; Sood, R; Bishop, K; Song, H; Andre, P; +5 Authors

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

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.

Keywords

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

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    selected citations
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    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    450
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 1%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 1%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 0.1%
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
450
Top 1%
Top 1%
Top 0.1%
hybrid