RRC ID 60045
Author Gunawan F, Gentile A, Fukuda R, Tsedeke AT, Jiménez-Amilburu V, Ramadass R, Iida A, Sehara-Fujisawa A, Stainier DYR.
Title Focal adhesions are essential to drive zebrafish heart valve morphogenesis.
Journal J Cell Biol
Abstract Elucidating the morphogenetic events that shape vertebrate heart valves, complex structures that prevent retrograde blood flow, is critical to understanding valvular development and aberrations. Here, we used the zebrafish atrioventricular (AV) valve to investigate these events in real time and at single-cell resolution. We report the initial events of collective migration of AV endocardial cells (ECs) into the extracellular matrix (ECM), and their subsequent rearrangements to form the leaflets. We functionally characterize integrin-based focal adhesions (FAs), critical mediators of cell-ECM interactions, during valve morphogenesis. Using transgenes to block FA signaling specifically in AV ECs as well as loss-of-function approaches, we show that FA signaling mediated by Integrin α5β1 and Talin1 promotes AV EC migration and overall shaping of the valve leaflets. Altogether, our investigation reveals the critical processes driving cardiac valve morphogenesis in vivo and establishes the zebrafish AV valve as a vertebrate model to study FA-regulated tissue morphogenesis.
Volume 218(3)
Pages 1039-1054
Published 2019-3-4
DOI 10.1083/jcb.201807175
PII jcb.201807175
PMID 30635353
PMC PMC6400548
MeSH Animals Cell Movement Endocardium / embryology* Extracellular Matrix / genetics Extracellular Matrix / metabolism Focal Adhesions / genetics Focal Adhesions / metabolism* Heart Valves / embryology* Integrin alpha5beta1 / genetics Integrin alpha5beta1 / metabolism Organogenesis* Signal Transduction* Talin / genetics Talin / metabolism Zebrafish / embryology* Zebrafish / genetics Zebrafish Proteins / genetics Zebrafish Proteins / metabolism
IF 8.891
Times Cited 9
Zebrafish itga5 kt451