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Effect of Vascular Cadherin Knockdown on Zebrafish Vasculature during Development

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-cadhe...

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Autores principales: Mitchell, Ian C., Brown, Timothy S., Terada, Lance S., Amatruda, James F., Nwariaku, Fiemu E.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2808391/
https://www.ncbi.nlm.nih.gov/pubmed/20098718
http://dx.doi.org/10.1371/journal.pone.0008807
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author Mitchell, Ian C.
Brown, Timothy S.
Terada, Lance S.
Amatruda, James F.
Nwariaku, Fiemu E.
author_facet Mitchell, Ian C.
Brown, Timothy S.
Terada, Lance S.
Amatruda, James F.
Nwariaku, Fiemu E.
author_sort Mitchell, Ian C.
collection PubMed
description 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.
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spelling pubmed-28083912010-01-23 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. PLoS One Research Article 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. Public Library of Science 2010-01-20 /pmc/articles/PMC2808391/ /pubmed/20098718 http://dx.doi.org/10.1371/journal.pone.0008807 Text en Mitchell et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Mitchell, Ian C.
Brown, Timothy S.
Terada, Lance S.
Amatruda, James F.
Nwariaku, Fiemu E.
Effect of Vascular Cadherin Knockdown on Zebrafish Vasculature during Development
title Effect of Vascular Cadherin Knockdown on Zebrafish Vasculature during Development
title_full Effect of Vascular Cadherin Knockdown on Zebrafish Vasculature during Development
title_fullStr Effect of Vascular Cadherin Knockdown on Zebrafish Vasculature during Development
title_full_unstemmed Effect of Vascular Cadherin Knockdown on Zebrafish Vasculature during Development
title_short Effect of Vascular Cadherin Knockdown on Zebrafish Vasculature during Development
title_sort effect of vascular cadherin knockdown on zebrafish vasculature during development
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2808391/
https://www.ncbi.nlm.nih.gov/pubmed/20098718
http://dx.doi.org/10.1371/journal.pone.0008807
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