Cardiac forces regulate zebrafish heart valve delamination by modulating Nfat signaling.
Fiche publication
Date publication
janvier 2022
Journal
PLoS biology
Auteurs
Membres identifiés du Cancéropôle Est :
Mme MESSADDEQ Nadia , Dr KLYMCHENKO Andrey
Tous les auteurs :
Chow RW, Fukui H, Chan WX, Tan KSJ, Roth S, Duchemin AL, Messaddeq N, Nakajima H, Liu F, Faggianelli-Conrozier N, Klymchenko AS, Choon Hwai Y, Mochizuki N, Vermot J
Lien Pubmed
Résumé
In the clinic, most cases of congenital heart valve defects are thought to arise through errors that occur after the endothelial-mesenchymal transition (EndoMT) stage of valve development. Although mechanical forces caused by heartbeat are essential modulators of cardiovascular development, their role in these later developmental events is poorly understood. To address this question, we used the zebrafish superior atrioventricular valve (AV) as a model. We found that cellularized cushions of the superior atrioventricular canal (AVC) morph into valve leaflets via mesenchymal-endothelial transition (MEndoT) and tissue sheet delamination. Defects in delamination result in thickened, hyperplastic valves, and reduced heart function. Mechanical, chemical, and genetic perturbation of cardiac forces showed that mechanical stimuli are important regulators of valve delamination. Mechanistically, we show that forces modulate Nfatc activity to control delamination. Together, our results establish the cellular and molecular signature of cardiac valve delamination in vivo and demonstrate the continuous regulatory role of mechanical forces and blood flow during valve formation.
Référence
PLoS Biol. 2022 Jan 14;20(1):e3001505