Research Article: Effect of Vascular Cadherin Knockdown on Zebrafish Vasculature during Development

Date Published: January 20, 2010

Publisher: Public Library of Science

Author(s): Ian C. Mitchell, Timothy S. Brown, Lance S. Terada, James F. Amatruda, Fiemu E. Nwariaku, Bruce Riley.

Abstract: Vascular endothelial cadherin (VE-cad) is essential for endothelial barrier integrity and vascular sprouting. However, the role of this important protein in cardiovascular development is only recently becoming apparent.

Partial Text: The formation of new blood vessels is a critical part of processes as diverse as wound healing, tumor growth and embryo development. The endothelial cells lining these vessels are bound to each other through both adherens junctions and tight junctions. Within the adherens junction, the most abundant protein present is the endothelial-specific vascular endothelial cadherin (VE-cad). While the extracellular portion of VE-cadherin is critical for endothelial cell adhesion, its short cytoplasmic tail also provides a link to the actin cytoskeleton through associated junctional proteins such as β-catenin, plakoglobin and p120 [1], [2]. The interaction between VE-cadherin and junctional proteins modulates endothelial cell activation and migration in response to growth factors. Exposure of cultured endothelial cells to growth factors and cytokines increases tyrosine phosphorylation of VE-cad, and increases endothelial permeability and migration [3], [4].

VE-cadherin is essential for endothelial cell-cell interaction and barrier integrity in vitro. Less is known about the in vivo role of this protein in cardiac and vascular development. Mice deficient in VE-cadherin manifest defective cardiac development, but it is unclear whether these defects are primarily due to the loss of VE-cadherin, or secondary to the concomitant severe vascular defects. In this study, we find that VE-cadherin knockdown does not directly affect vessel development, yet leads to profound structural and functional cardiac defects in zebrafish embryos.



0 0 vote
Article Rating
Notify of
Inline Feedbacks
View all comments