Mechanical Stress Regulates Epithelial Tissue Integrity and Stiffness through the FGFR/Erk2 Signaling Pathway during Embryogenesis. Author Noriyuki Kinoshita, Yutaka Hashimoto, Naoko Yasue, Makoto Suzuki, Ileana Cristea, Naoto Ueno Publication Year 2020 Type Journal Article Abstract Physical forces generated by tissue-tissue interactions are a critical component of embryogenesis, aiding the formation of organs in a coordinated manner. In this study, using Xenopus laevis embryos and phosphoproteome analyses, we uncover the rapid activation of the mitogen-activated protein (MAP) kinase Erk2 upon stimulation with centrifugal, compression, or stretching force. We demonstrate that Erk2 induces the remodeling of cytoskeletal proteins, including F-actin, an embryonic cadherin C-cadherin, and the tight junction protein ZO-1. We show these force-dependent changes to be prerequisites for the enhancement of cellular junctions and tissue stiffening during early embryogenesis. Furthermore, Erk2 activation is FGFR1 dependent while not requiring fibroblast growth factor (FGF) ligands, suggesting that cell/tissue deformation triggers receptor activation in the absence of ligands. These findings establish previously unrecognized functions for mechanical forces in embryogenesis and reveal its underlying force-induced signaling pathways. Keywords Animals, Biomechanical Phenomena, Signal Transduction, Phosphorylation, Stress, Mechanical, Embryonic Development, Xenopus laevis, Epithelium, Gastrulation, Intercellular Junctions, Mitogen-Activated Protein Kinase 1, Receptor, Fibroblast Growth Factor, Type 1 Journal Cell Rep Volume 30 Issue 11 Pages 3875-3888.e3 Date Published 2020 Mar 17 ISSN Number 2211-1247 DOI 10.1016/j.celrep.2020.02.074 Alternate Journal Cell Rep PMID 32187556 PubMedGoogle ScholarBibTeXEndNote X3 XML