Vegfa signaling regulates diverse artery/vein formation in vertebrate vasculatures
Vegfa signaling regulates diverse artery/vein formation in vertebrate vasculatures
复制标题
Vegfa 信号调节脊椎动物脉管系统中不同动脉/静脉的形成
DOI：
10.1016/j.jgg.2017.07.005
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发表时间：
2017-10-20
影响因子：
5.9
通讯作者：
Zhong, Tao P.
中科院分区：
文献类型：
--
作者：
Jin, Daqing;Zhu, Diqi;Zhong, Tao P.
血管内皮生长因子A(VEGFA)信号调节胚胎发育和器官形成过程中的血管发育。然而，控制不同组织中各种动脉/静脉形成的信号机制还不完全清楚。在本研究中，我们利用转录激活物样效应核酸酶(TALEN)来产生斑马鱼蔬菜突变体。VEGFAA(-/-)胚胎是胚胎致命的，表现为背主动脉(DA)的完全丧失和主静脉的扩张。在主干中轴血管的血管生成过程中，VEGFA信号的激活以牺牲静脉细胞为代价，扩大了动脉细胞的数量。血管内皮生长因子(VEGFA)信号转导调控动静脉规范后内皮细胞(EC)的增殖。VEGFA的缺乏和过度表达抑制了顶端细胞丝状足的形成，干扰了节间血管(ISV)的寻径。在头部血管系统中，VEGFAA(-/-)会导致一对中脑静脉(MSVS)和中央动脉(CTA)的丧失，这两者通常都是通过萌芽的血管生成来发展的。我们的结果表明，VEGFA信号在躯干血管形成过程中以牺牲主静脉为代价诱导DA的形成，并且VEGFA是脑内MSVS和CTA血管形成所必需的。这些发现表明，在脊椎动物的血管系统中，Vegfa信号通过不同的细胞机制调控不同的动脉/静脉的形成。版权所有(C)2017，中国科学院遗传与发育生物学研究所，中国遗传学会。爱思唯尔有限公司和科学出版社出版。版权所有。
Vascular endothelial growth factor A (Vegfa) signaling regulates vascular development during embryogenesis and organ formation. However, the signaling mechanisms that govern the formation of various arteries/veins in various tissues are incompletely understood. In this study, we utilized transcription activator-like effector nuclease (TALEN) to generate zebrafish vegfaa mutants. vegfaa(-/-) embryos are embryonic lethal, and display a complete loss of the dorsal aorta (DA) and expansion of the cardinal vein. Activation of Vegfa signaling expands the arterial cell population at the expense of venous cells during vasculogenesis of the axial vessels in the trunk. Vegfa signaling regulates endothelial cell (EC) proliferation after arterial-venous specification. Vegfa deficiency and overexpression inhibit the formation of tip cell filopodia and interfere with the pathfinding of intersegmental vessels (ISVs). In the head vasculature, vegfaa(-/-) causes loss of a pair of mesencephalic veins (MsVs) and central arteries (CtAs), both of which usually develop via sprouting angiogenesis. Our results indicate that Vegfa signaling induces the formation of the DA at the expense of the cardinal vein during the trunk vasculogenesis, and that Vegfa is required for the angiogenic formation of MsVs and CtAs in the brain. These findings suggest that Vegfa signaling governs the formation of diverse arteries/veins by distinct cellular mechanisms in vertebrate vasculatures. Copyright (C) 2017, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Limited and Science Press. All rights reserved.