Zebrafish neuropilins are differentially expressed and interact with vascular endothelial growth factor during embryonic vascular development
Zebrafish neuropilins are differentially expressed and interact with vascular endothelial growth factor during embryonic vascular development
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DOI：
10.1002/dvdy.20048
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发表时间：
2004-09-01
影响因子：
2.5
通讯作者：
Schulte-Merker, S
中科院分区：
文献类型：
--
作者：
Martyn, U;Schulte-Merker, S
神经纤毛蛋白1（Nrp1）和神经纤毛蛋白2（Nrp2）是在几种脊椎动物中鉴定的非激酶血管内皮生长因子受体（VEGFR），其作为受体酪氨酸激酶VEGFR1和VEGFR2的共受体起作用。我们确定了四个斑马鱼nrp基因，nrp1a，nrp1b，nrp2a，和nrp2b，并表征其在血管发育中的功能。我们发现，所有的nrp基因显示不同的表达模式，nrp1a和nrp1b在背主动脉中表达，而nrp2a和nrp2b转录本可以检测到在该地区的后主静脉。敲除nrp1a、nrp1b和nrp2a导致不正确的动静脉连接和不规则的节段间血管模式，表明这些Nrps在相同的过程中起作用。nrp2b基因敲除还导致血管畸形和心包缺损。此外，我们提供的证据表明，新发现的Nrps协同相互作用与VEGF在体内。两者合计，我们的研究结果表明，在斑马鱼，所有四个neuropilins参与VEGF介导的血管发育。(C)2004 Wiley-Liss，Inc.
Neuropilin1 (Nrp1) and Neuropilin2 (Nrp2) are nonkinase vascular endothelial growth factor receptors (VEGFR) identified in several vertebrates, which function as coreceptors for the receptor tyrosine kinases VEGFR1 and VEGFR2. We identified four zebrafish nrp genes, nrp1a, nrp1b, nrp2a, and nrp2b, and characterized their function in vascular development. We show that all nrp genes display distinct expression patterns and that nrp1a and nrp1b are expressed in the dorsal aorta, while nrp2a and nrp2b transcripts could be detected in the region of the posterior cardinal vein. Knockdown of nrp1a, nrp1b, and nrp2a resulted in improper arteriovenous connections and irregular intersegmental vessel patterning, indicating that these Nrps function in the same process. Nrp2b knockdown also caused vessel malformations and a pericardial defect. In addition, we provide evidence that the newly identified Nrps synergistically interact with VEGF in vivo. Taken together, our results show that, in zebrafish, all four neuropilins are involved in VEGF-mediated vessel development. (C) 2004 Wiley-Liss, Inc.