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ZFIN ID: ZDB-PUB-190418-15
The transmembrane protein Crb2a regulates cardiomyocyte apicobasal polarity and adhesion in zebrafish
Jiménez-Amilburu, V., Stainier, D.Y.R.
Date: 2019
Source: Development (Cambridge, England)   146(9): (Journal)
Registered Authors: Stainier, Didier
Keywords: Adhesion, Apicobasal polarity, Cardiac trabeculation, Crumbs, Junctions
MeSH Terms:
  • Animals
  • Cell Adhesion/genetics
  • Cell Adhesion/physiology
  • Cell Polarity/genetics
  • Cell Polarity/physiology
  • Membrane Proteins/genetics
  • Membrane Proteins/metabolism*
  • Myocytes, Cardiac/cytology
  • Myocytes, Cardiac/metabolism*
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Zonula Occludens-1 Protein/genetics
  • Zonula Occludens-1 Protein/metabolism*
PubMed: 30992276 Full text @ Development
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 and colocalizes with the junctional protein ZO-1. Subsequently, Crb2a becomes localized all along the apical membrane of compact layer cardiomyocytes and is downregulated in the delaminating cardiomyocytes. We show that blood flow and Nrg/ErbB2 signaling regulate Crb2a localization dynamics. crb2a-/- 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 junction proteins in cardiomyocytes. Importantly, transplantation data show that Crb2a controls CM behavior in a cell-autonomous manner in the sense that crb2a-/- cardiomyocytes transplanted into wild-type animals were always found in the trabecular layer. Altogether, our study reveals a critical role for Crb2a during cardiac development.