Effect of vascular cadherin knockdown on zebrafish vasculature during development

Ian C. Mitchell, Timothy S. Brown, Lance S. Terada, James F. Amatruda, Fiemu E. Nwariaku

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Background: 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. Methodology/Principal Findings: To characterize the role of VE-cadherin in cardiovascular development, we analyzed cardiovascular development in a zebrafish VE-cad knockdown model. Embryos deficient in VE-cad show profoundly impaired cardiac development despite having apparently normal peripheral vasculature. Initial formation of the heart proceeds normally in knockdown embryos, but subsequent looping morphogenesis is impaired. Consistent with these results, VE-cad knockdown embryos demonstrate impaired cardiac function and early circulatory arrest. Histologic examination of knockdown embryos shows persistent, abnormal separation of the endocardial and myocardial layers. Using transmission electron microscopy, we demonstrate that endocardial junctions form poorly in VE-cad knockdown embryos, with resulting leak across the endothelial layer and reduction in the density of the cardiac jelly. Conclusions: Our results demonstrate a significant role for VE-cadherin in cardiac development independent of its effects on the formation of the peripheral vasculature.

Original languageEnglish (US)
Article numbere8807
JournalPloS one
Volume5
Issue number1
DOIs
StatePublished - Jan 20 2010

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • General Agricultural and Biological Sciences
  • General

Fingerprint

Dive into the research topics of 'Effect of vascular cadherin knockdown on zebrafish vasculature during development'. Together they form a unique fingerprint.

Cite this