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Title: Focal adhesions are essential to drive zebrafish heart valve morphogenesis
Authors: Gunawan, Felix
Gentile, Alessandra
Fukuda, Ryuichi
Tsedeke, Ayele Taddese
Jiménez-Amilburu, Vanesa
Ramadass, Radhan
Iida, Atsuo  kyouindb  KAKEN_id
Sehara-Fujisawa, Atsuko
Stainier, Didier Y.R.
Author's alias: 飯田, 敦夫
瀬原, 淳子
Issue Date: 4-Mar-2019
Publisher: Rockefeller University Press
Journal title: Journal of Cell Biology
Volume: 218
Issue: 3
Start page: 1039
End page: 1054
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.
Rights: © 2019 Gunawan et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
URI: http://hdl.handle.net/2433/237392
DOI(Published Version): 10.1083/jcb.201807175
PubMed ID: 30635353
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