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 journalArticle

21 Citations (Scopus)

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

Fingerprint

cadherins
Zebrafish
Cadherins
Danio rerio
blood vessels
Blood Vessels
embryo (animal)
Embryonic Structures
jellies
cardiac output
cadherin 5
sprouting
Transmission Electron Microscopy
Morphogenesis
morphogenesis
transmission electron microscopy
heart
Transmission electron microscopy

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Effect of vascular cadherin knockdown on zebrafish vasculature during development. / Mitchell, Ian C.; Brown, Timothy S.; Terada, Lance S.; Amatruda, James F.; Nwariaku, Fiemu E.

In: PLoS One, Vol. 5, No. 1, e8807, 20.01.2010.

Research output: Contribution to journalArticle

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AU - Amatruda, James F.

AU - Nwariaku, Fiemu E.

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