Distinct and redundant functions of Esama and VE-cadherin during vascular morphogenesis

Development. 2017 Apr 15;144(8):1554-1565. doi: 10.1242/dev.140038. Epub 2017 Mar 6.

Abstract

The cardiovascular system forms during early embryogenesis and adapts to embryonic growth by sprouting angiogenesis and vascular remodeling. These processes require fine-tuning of cell-cell adhesion to maintain and re-establish endothelial contacts, while allowing cell motility. We have compared the contribution of two endothelial cell-specific adhesion proteins, VE-cadherin (VE-cad/Cdh5) and Esama (endothelial cell-selective adhesion molecule a), during angiogenic sprouting and blood vessel fusion (anastomosis) in the zebrafish embryo by genetic analyses. Different combinations of mutant alleles can be placed into a phenotypic series with increasing defects in filopodial contact formation. Contact formation in esama mutants appears similar to wild type, whereas esama-/-; ve-cad+/- and ve-cad single mutants exhibit intermediate phenotypes. The lack of both proteins interrupts filopodial interaction completely. Furthermore, double mutants do not form a stable endothelial monolayer, and display intrajunctional gaps, dislocalization of Zo-1 and defects in apical-basal polarization. In summary, VE-cadherin and Esama have distinct and redundant functions during blood vessel morphogenesis, and both adhesion proteins are central to endothelial cell recognition during anastomosis.

Keywords: Anastomosis; Angiogenesis; Cdh5; Cell adhesion; Cell contact formation; Endothelial cell; Esam; Morphogenesis; VE-cadherin; Zebrafish.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism*
  • Blood Vessels / embryology*
  • Blood Vessels / metabolism*
  • Cadherins / metabolism*
  • Cell Adhesion Molecules / metabolism*
  • Cell Communication
  • Cell Polarity
  • Endothelial Cells / cytology
  • Endothelial Cells / metabolism
  • Intercellular Junctions / metabolism
  • Morphogenesis*
  • Mutation / genetics
  • Neovascularization, Physiologic*
  • Pseudopodia / metabolism
  • Zebrafish / embryology*
  • Zebrafish / metabolism*
  • Zebrafish Proteins / metabolism*

Substances

  • Antigens, CD
  • Cadherins
  • Cell Adhesion Molecules
  • Zebrafish Proteins
  • cadherin 5