Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, Fujishirodai 5-7-1, Suita, Osaka 565-8565, Japan.
Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, Fujishirodai 5-7-1, Suita, Osaka 565-8565, Japan.
Dev Cell. 2015 Jan 12;32(1):109-22. doi: 10.1016/j.devcel.2014.11.024.
During angiogenesis in vivo, endothelial cells (ECs) at the tips of vascular sprouts actively extend filopodia that are filled with bundles of linear actin filaments. To date, signaling pathways involved in the formation of endothelial filopodia have been studied using in-vitro-cultured ECs that behave differently from those in vivo. Herein, we have delineated a signaling pathway that governs the assembly of endothelial filopodia during angiogenic sprouting of the caudal vein plexus (CVP) in zebrafish. During CVP formation, bone morphogenetic protein induces the extension of endothelial filopodia and their migration via Arhgef9b-mediated activation of Cdc42. Active Cdc42 binds to and stimulates Formin-like 3, an actin-regulatory protein of the formin family, which, in turn, promotes the extension of endothelial filopodia to facilitate angiogenic sprouting of the CVP. Thus, this study has elucidated molecular mechanisms underlying the formation of endothelial filopodia and their role in angiogenesis in vivo.
在体内血管生成过程中，血管芽尖端的内皮细胞 (EC) 会积极伸出充满线性肌动蛋白丝束的丝状伪足。迄今为止，已经使用体外培养的 EC 研究了参与内皮细胞丝状伪足形成的信号通路，这些通路与体内的 EC 表现不同。在此，我们描绘了一个信号通路，该通路控制斑马鱼尾静脉丛 (CVP) 血管生成芽中内皮细胞丝状伪足的组装。在 CVP 形成过程中，骨形态发生蛋白诱导内皮细胞丝状伪足的延伸及其通过 Arhgef9b 介导的 Cdc42 激活的迁移。活性 Cdc42 与 Formin-like 3 结合并刺激其活性，Formin-like 3 是一种属于formin 家族的肌动蛋白调节蛋白，它反过来促进内皮细胞丝状伪足的延伸，从而促进 CVP 的血管生成芽出。因此，这项研究阐明了内皮细胞丝状伪足形成的分子机制及其在体内血管生成中的作用。
