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.

Nature Communications
|August 5, 2025
PubMed

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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