The transmembrane protein Crb2a regulates cardiomyocyte apicobasal polarity and adhesion in zebrafish

Abstract

Tissue morphogenesis requires changes in cell-cell adhesion as well as in cell shape and polarity. Cardiac trabeculation is a morphogenetic process essential to form a functional ventricular wall. Here we show that zebrafish hearts lacking Crb2a, a component of the Crumbs polarity complex, display compact wall integrity defects and fail to form trabeculae. Crb2a localization is very dynamic, at a time when other cardiomyocyte junctional proteins also relocalize. Before the initiation of cardiomyocyte delamination to form the trabecular layer, Crb2a is expressed in all ventricular cardiomyocytes colocalizing with the junctional protein ZO-1. Subsequently, Crb2a becomes localized all along the apical membrane of compact layer cardiomyocytes and is downregulated by those delaminating. We show that blood flow and Nrg/ErbB2 signaling regulate these Crb2a localization changes. crb2a mutants display a multilayered wall with polarized cardiomyocytes, a unique phenotype. Our data further indicate that Crb2a regulates cardiac trabeculation by controlling the localization of tight and adherens junctions in cardiomyocytes. Importantly, transplantation data show that Crb2a controls trabeculation in a CM-autonomous manner. Altogether, our study reveals a critical role for Crb2a during cardiac development.\n\nSummary statementInvestigation of the Crumbs polarity protein Crb2a in zebrafish reveals a novel role in cardiac development via regulation of cell-cell adhesion and apicobasal polarity.