Faculty of Biology, Cell Signaling and Dynamics, Philipps-University of Marburg, Marburg, Germany.
Organogenesis and Cancer Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Sci Adv. 2024 Jul 5;10(27):eadk1174. doi: 10.1126/sciadv.adk1174.
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 -expressing neural progenitor cell population in the dorsal neural tube. Vascular tip cells exhibit directed elongation and migration toward and along the -expressing neural progenitor cells. Notably, restoration of neural but not vascular expression in 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.
在血管生成过程中，血管尖端细胞引导新生血管芽形成血管网络。Apelin 是 G 蛋白偶联受体 Aplnr 的激动剂，富含于血管尖端细胞中，据推测血管衍生的 Apelin 调节发芽血管生成。我们在背侧神经管中鉴定出表达的神经祖细胞群体。血管尖端细胞表现出定向伸长和迁移，朝向并沿着表达的神经祖细胞。值得注意的是，在突变体中恢复神经但不是血管表达可纠正突变体的血管生成缺陷。通过功能分析，我们显示 Apelin 信号对尖端细胞行为（如丝状伪足形成和细胞伸长）的需求。通过遗传相互作用研究和转基因活性报告分析，我们确定 Apelin 信号是体内尖端细胞中磷酸肌醇 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，Apelin 信号介导了以前未被识别的神经血管相互作用，这对于发芽血管生成过程中的尖端细胞功能很重要。
