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

Abstract

Summary 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.. CC-BY-NC-ND 4.0 International license It is made available under a (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/398909 doi: bioRxiv preprint first posted online Aug. 23, 2018; 3 AbstractTissue 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.

Crumbs2 mediates ventricular layer remodelling to form the adult spinal cord central canal

“…In invertebrates, Par and Crumbs proteins directly interact to determine the apicobasal axis and the position and stability of cell-cell adherens junctions (Wodarz et al, 1995;Klebes and Knust, 2000;Assemat et al;Bulgakova and Knust, 2009;reviewed in Pichaud, 2019). Par and Crumbs complex components are evolutionarily conserved, and similarly regulate polarity and integrity of vertebrate epithelia and neuroepithelia (reviewed in McCaffrey and Macara, 2011;Nikolopoulou et al, 2018); in the mouse telencephalon, CRB2 is required for maintenance of the apical polarity complex (Dudok et al, 2016) and in zebrafish, Crb2a controls the localization of tight and adherens junction proteins in cardiomyocytes (Jiménez-Amilburu and Stainier et al, 2019). Apical complexes play a central role in early stages of neural tube formation (reviewed in Cearns et al, 2016).…”

The role of extracellular matrix in zebrafish cardiac development and regeneration

“…These experiments still remain to be performed and could provide novel insight into more subtle phenotypes masked by the laminin dependent effects. (Gentile et al, 2021;Gunawan et al, 2021;Jimenez Amilburu, 2018;Jiménez-Amilburu et al, 2016;Jiménez-Amilburu & Stainier, 2019;Priya et al, 2020;Sun et al, 2021). These processes occur during essential developmental phases such as cardiac trabeculation and valvulogenesis (Jimenez Amilburu, 2018;Jiménez-Amilburu et al, 2016;Jiménez-Amilburu & Stainier, 2019;Lee & Streuli, 2014;Rasouli & Stainier, 2017;Uribe et al, 2018;Wu, 2018).…”