Wnt Signaling Gradients Establish Planar Cell Polarity by Inducing Vangl2 Phosphorylation through Ror2
| Autor: | James Robinson, Hai Song, Aris N. Economides, Bo Gao, Milton A. English, Philipp Andre, Yingzi Yang, Lisa Garrett, Kevin Bishop, Yasuhiro Minami, Gene Elliot, Raman Sood |
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| Rok vydání: | 2011 |
| Předmět: |
Receptor complex
Cellular polarity Receptor tyrosine kinase-like orphan receptor Embryonic Development Nerve Tissue Proteins Biology Receptor Tyrosine Kinase-like Orphan Receptors Models Biological General Biochemistry Genetics and Molecular Biology Wnt-5a Protein Mice Cell polarity Animals Phosphorylation Molecular Biology beta Catenin Wnt signaling pathway Cell Polarity ROR2 Cell Biology Fibroblasts Cell biology body regions Wnt Proteins Protein Transport Morphogen Protein Binding Signal Transduction Developmental Biology |
| Zdroj: | Developmental Cell. 20(2):163-176 |
| ISSN: | 1534-5807 |
| DOI: | 10.1016/j.devcel.2011.01.001 |
| Popis: | SummaryIt 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. |
| Databáze: | OpenAIRE |
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