Distinct genetic interactions between multiple Vegf receptors are required for development of different blood vessel types in zebrafish
Distinct genetic interactions between multiple Vegf receptors are required for development of different blood vessel types in zebrafish
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DOI：
10.1073/pnas.0506886103
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发表时间：
2006-04-25
影响因子：
11.1
通讯作者：
Lawson, ND
中科院分区：
文献类型：
--
作者：
Covassin, LD;Villefranc, JA;Lawson, ND
最近的证据表明，血管内皮生长因子a （Vegfa）在斑马鱼和小鼠胚胎的动脉发育过程中起着特定的作用，而对控制静脉形成的信号知之甚少。在斑马鱼中，vegfa的缺失阻断了节段动脉的形成并降低了动脉特异性基因的表达，而静脉在很大程度上不受影响。在这里，我们描述了斑马鱼vegf受体-2同源物kdra的突变，该突变消除了其激酶活性并导致动脉发育中的特定缺陷。我们进一步发现，Vegfc受体Flt4在动脉形态发生过程中与Kdr合作，但不参与分化。我们还发现了一个额外的斑马鱼vegfr-2同源物，称为kdrb，它可以部分补偿kdra的损失，但对于野生型胚胎的血管发育是必不可少的。有趣的是，我们发现这些Vegf受体也是静脉形成所必需的，但与动脉发育所需的基因相互作用不同。综上所述，我们的研究结果表明，胚胎中动脉和静脉的形成部分受不同的Vegf受体组合的控制，并提示在脊椎动物发育过程中产生血管多样性的遗传机制。
Recent evidence indicates a specific role for vascular endothelial growth factor a (Vegfa) during artery development in both zebrafish and mouse embryos, whereas less is known about signals that govern vein formation. In zebrafish, loss of vegfa blocks segmental artery formation and reduces artery-specific gene expression, whereas veins are largely unaffected. Here, we describe a mutation in the zebrafish vegf receptor-2 homolog, kdra, which eliminates its kinase activity and leads to specific defects in artery development. We further find that Flt4, a receptor for Vegfc, cooperates with Kdr during artery morphogenesis, but not differentiation. We also identify an additional zebrafish vegfr-2 ortholog, referred to as kdrb, which can partially compensate for loss of kdra but is dispensable for vascular development in wild-type embryos. interestingly, we find that these Vegf receptors are also required for formation of veins but in distinct genetic interactions that differ from those required for artery development. Taken together, our results indicate that formation of arteries and veins in the embryo is governed in part by different Vegf receptor combinations and suggest a genetic mechanism for generating blood vessel diversity during vertebrate development.