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.


RESULTS
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.
Mitchell
Ian C
IC
Division of Gastrointestinal and Endocrine Surgery, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
Brown
Timothy S
TS
Terada
Lance S
LS
Amatruda
James F
JF
Nwariaku
Fiemu E
FE
D000818:Animals; D030801:Animals, Genetically Modified; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D001808:Blood Vessels / Q000196:embryology* / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers; D055785:Gene Knockdown Techniques; D017403:In Situ Hybridization; D015027:Zebrafish / Q000196:embryology*; D000099152:Cadherin 5
D015703:Antigens, CD; D015820:Cadherins; D017931:DNA Primers; D000099152:Cadherin 5