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Published on: October 1, 2007
FGF receptor modulates planar cell polarity in the neuroectoderm via Vangl2 tyrosine phosphorylation
Ilya Chuykin1, Sergei Y Sokol2
1Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, USA.
Abstract:
FGF receptors play pivotal roles in morphogenetic processes, including vertebrate neurulation. Planar cell polarity signaling coordinates cell orientation in the tissue plane and is essential for neural tube closure. Here, we demonstrate abnormal planar polarity in the Xenopus neuroectoderm depleted of FGFR1, suggesting a mechanistic connection between FGFR signaling and morphogenesis. FGFR1 associates with the core planar cell polarity protein Vangl2, leading to its phosphorylation at N-terminal tyrosines, a modification also induced by FGF8. Vangl2 phosphorylation requires FGFR1 activity in Xenopus embryos and mouse embryonic stem cells, extending our observations to mammals. A non-phosphorylatable Vangl2 construct exhibits increased binding to the receptor tyrosine kinase PTK7, suggesting a potential role of Vangl2 phosphorylation. By contrast, a phosphomimetic Vangl2 mutant shows reduced interactions with Prickle and PTK7, and disrupted planar polarity in the neuroectoderm. Together, these findings identify cross-talk between the FGFR1 and planar cell polarity pathways mediated by Vangl2 tyrosine phosphorylation.
Insights
Fibroblast Growth Factor Receptor 1 (FGFR1) signaling impacts planar cell polarity during vertebrate neural tube development. FGFR1 phosphorylates Vangl2, a key protein in cell orientation, revealing cross-talk essential for morphogenesis.
Area of Science:
- Developmental Biology
- Cell Signaling
- Molecular Biology
Background:
- Fibroblast Growth Factor Receptors (FGFRs) are crucial for embryonic development and morphogenesis.
- Planar Cell Polarity (PCP) signaling directs cell orientation within tissues and is vital for vertebrate neural tube closure.
Purpose of the Study:
- To investigate the mechanistic link between FGFR signaling and PCP during Xenopus neurulation.
- To elucidate how FGFR1 activity influences Vangl2, a core PCP protein.
Main Methods:
- Depletion of FGFR1 in Xenopus embryos to observe effects on neuroectoderm planar polarity.
- Co-immunoprecipitation assays to study the interaction and phosphorylation of Vangl2 by FGFR1.
- Analysis of Vangl2 mutants (non-phosphorylatable and phosphomimetic) in Xenopus and mouse embryonic stem cells.
Main Results:
- FGFR1 depletion caused abnormal planar polarity in Xenopus neuroectoderm.
- FGFR1 directly associates with and phosphorylates Vangl2 at specific tyrosine residues.
- Vangl2 phosphorylation by FGFR1 affects its interaction with PTK7 and Prickle, impacting planar polarity.
Conclusions:
- FGFR1 signaling pathway directly intersects with the planar cell polarity pathway through Vangl2 tyrosine phosphorylation.
- This cross-talk is conserved from Xenopus to mammals, highlighting its fundamental role in vertebrate development.
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