PDF(Pubmed)
Abstract：
During angiogenesis, vascular tip cells guide nascent vascular sprouts to form a vascular network. Apelin, an agonist of the G protein-coupled receptor Aplnr, is enriched in vascular tip cells, and it is hypothesized that vascular-derived Apelin regulates sprouting angiogenesis. We identify an apelin-expressing neural progenitor cell population in the dorsal neural tube. Vascular tip cells exhibit directed elongation and migration toward and along the apelin-expressing neural progenitor cells. Notably, restoration of neural but not vascular apelin expression in apelin mutants remedies the angiogenic defects of mutants. By functional analyses, we show the requirement of Apelin signaling for tip cell behaviors, like filopodia formation and cell elongation. Through genetic interaction studies and analysis of transgenic activity reporters, we identify Apelin signaling as a modulator of phosphoinositide 3-kinase and extracellular signal-regulated kinase signaling in tip cells in vivo. Our results suggest a previously unidentified neurovascular cross-talk mediated by Apelin signaling that is important for tip cell function during sprouting angiogenesis.
摘要：
在血管生成过程中,血管尖细胞引导新生的血管芽形成血管网。Apelin,G蛋白偶联受体Aplnr的激动剂，富含血管尖端细胞，据推测，血管来源的Apelin调节发芽血管生成。我们在背侧神经管中鉴定了表达apelin的神经祖细胞群。血管尖端细胞表现出朝向和沿着表达apelin的神经祖细胞的定向伸长和迁移。值得注意的是,在apelin突变体中恢复神经而不是血管apelin表达可以弥补突变体的血管生成缺陷。通过功能分析，我们展示了Apelin信号传导对尖端细胞行为的需求，比如丝足形成和细胞伸长。通过遗传相互作用研究和转基因活性报告基因分析，我们确定Apelin信号是体内tip细胞中磷酸肌醇3激酶和细胞外信号调节激酶信号的调节剂。我们的结果表明，由Apelin信号介导的先前未发现的神经血管串扰，这对于发芽血管生成期间的尖端细胞功能很重要。
