Mechanical Stress Regulates Epithelial Tissue Integrity and Stiffness through the FGFR/Erk2 Signaling Pathway during Embryogenesis

• Published in: Cell reports (Cambridge) 2020-03, Vol.30 (11), p.3875-3888.e3
• Main Authors: Kinoshita, Noriyuki, Hashimoto, Yutaka, Yasue, Naoko, Suzuki, Makoto, Cristea, Ileana M., Ueno, Naoto
• Format: Article
• Language: English
• Subjects: Animals; Biomechanical Phenomena; cell junction; Embryonic Development; Epithelium - physiology; ERK2; FGF receptor; Gastrulation; Intercellular Junctions - metabolism; MAPK1; mechanobiology; mechanosensing; Mitogen-Activated Protein Kinase 1 - metabolism; Phosphorylation; Receptor, Fibroblast Growth Factor, Type 1 - metabolism; Signal Transduction; stiffness; Stress, Mechanical; Xenopus laevis; Xenopus laevis - embryology; Xenopus laevis - physiology
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2020.02.074

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. [Display omitted] •Stretching of the ectodermal tissue of the Xenopus embryo activates Erk2•The stretch force phosphorylates Erk2 through FGFR in a ligand-independent manner•Force-induced FGFR/Erk2 signaling enhances apical junctional structures•This system increases epithelial stiffness and integrity during gastrulation Physical forces generated by morphogenetic movements are a critical component of embryogenesis. In this study, Kinoshita et al. demonstrate that stretching of the ectodermal tissue of the Xenopus embryo activates the FGF receptor/Erk2 pathway, which in turn enhances the apical junctional structure and increases epithelial stiffness and integrity during gastrulation.