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

Abstract

FGF receptors (FGFR) play pivotal roles in morphogenetic processes including vertebrate neurulation. Planar cell polarity (PCP) signaling coordinates cell polarization in tissue plane and also plays an essential role in neural tube closure. Here we demonstrate abnormal PCP in Xenopus neuroectoderm depleted of FGFR1, suggesting a mechanistic connection between FGFR signaling and morphogenesis. FGFR1 associated with the core PCP protein Vangl2 leading to its phosphorylation at N-terminal tyrosine residues. This phosphorylation required FGFR1 activity in frog embryos and mouse embryonic stem cells, extending our observations to mammals. Mutagenesis indicated that the phosphorylation inhibits the interaction of Vangl2 with Prickle and the receptor tyrosine kinase PTK7, leading to the disruption of neuroectodermal PCP. This study identifies a cross-talk between the FGFR and PCP pathways mediated by Vangl2 tyrosine phosphorylation.