Neuropilin-1 conveys semaphorin and VEGF signaling during neural and cardiovascular development
Neuropilin-1 conveys semaphorin and VEGF signaling during neural and cardiovascular development
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DOI：
10.1016/s1534-5807(03)00169-2
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发表时间：
2003-07-01
影响因子：
11.8
通讯作者：
Ginty, DD
中科院分区：
文献类型：
--
作者：
Gu, CH;Rodriguez, ER;Ginty, DD
神经纤毛蛋白-1（Npn-1）是一种结合来自结构不同家族的多种配体的受体，包括分泌型脑信号蛋白（Sema）和血管内皮生长因子（VEGF）。我们产生了npn-1敲入小鼠，其表达Npn-1的改变的配体结合位点变体，和npn-1条件无效小鼠，以建立Npn-1功能在发育中的心血管和神经系统中的细胞类型和配体特异性。我们的研究结果表明，血管内皮细胞中的VEGF-Npn-1信号是血管生成所必需的。与此形成鲜明对比的是，Sema-Npn-1信号传导对于一般血管发育不是必需的，但对于CNS和PNS中的几个神经元群体的轴突寻路是必需的。值得注意的是，Sema-Npn-1信号和VEGF-Npn-1信号对心脏发育至关重要。因此，Npn-1是一种多功能受体，在心脏、脉管系统和神经系统的发育过程中介导结构上不同的配体的活性。
Neuropilin-1 (Npn-1) is a receptor that binds multiple ligands from structurally distinct families, including secreted semaphorins (Sema) and vascular endothelial growth factors (VEGF). We generated npn-1 knockin mice, which express an altered ligand binding site variant of Npn-1, and npn-1 conditional null mice to establish the cell-type- and ligand specificity of Npn-1 function in the developing cardiovascular and nervous systems. Our results show that VEGF-Npn-1 signaling in endothelial cells is required for angiogenesis. In striking contrast, Sema-Npn-1 signaling is not essential for general vascular development but is required for axonal pathfinding by several populations of neurons in the CNS and PNS. Remarkably, both Sema-Npn-1 signaling and VEGF-Npn-1 signaling are critical for heart development. Therefore, Npn-1 is a multifunctional receptor that mediates the activities of structurally distinct ligands during development of the heart, vasculature, and nervous system.