Nat Commun 2025 Aug 05;161:7219. doi: 10.1038/s41467-025-62400-x.

FGF receptor modulates planar cell polarity in the neuroectoderm via Vangl2 tyrosine phosphorylation.

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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.

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