Effect of vascular cadherin knockdown on zebrafish vasculature during development.

Effect of vascular cadherin knockdown on zebrafish vasculature during development.
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DOI:
10.1371/journal.pone.0008807
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发表时间:
2010-01-20
期刊:
影响因子:
3.7
通讯作者:
Nwariaku FE
Nwariaku FE
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Mitchell IC;Brown TS;Terada LS;Amatruda JF;Nwariaku FE

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血管内皮钙粘蛋白(VE-cad)对内皮屏障完整性和血管发芽至关重要。然而,这种重要蛋白质在心血管发育中的作用直到最近才变得明显。为了描述VE-cadherin在心血管发育中的作用,我们分析了斑马鱼VE-cad敲低模型的心血管发育。缺乏VE-cad的胚胎显示心脏发育严重受损,尽管周围血管系统明显正常。在基因敲低的胚胎中,心脏的初始形成正常进行,但随后的环状形态发生受损。与这些结果一致,VE-cad基因敲低的胚胎表现出心脏功能受损和早期循环骤停。敲除胚胎的组织学检查显示心内膜和心肌层持续的异常分离。通过透射电镜,我们发现在VE-cad基因敲低的胚胎中,心内膜连接形成不良,导致内皮层渗漏和心脏果冻密度降低。我们的研究结果表明,ve -钙粘蛋白在心脏发育中的重要作用独立于其对周围血管形成的影响。
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. 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. 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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