Angiogenesis and vascular remodeling are essential for the establishment of vascular networks during organogenesis. Here we show that the Hippo signaling pathway effectors YAP and TAZ are required, in a gene dosage-dependent manner, for the proliferation and migration of vascular endothelial cells (ECs) during retinal angiogenesis. Intriguingly, nuclear translocation of YAP and TAZ induced by Lats1/2-deletion blocked endothelial migration and phenocopied Yap/Taz-deficient mutants. Furthermore, overexpression of a cytoplasmic form of YAP (YAPS127D) partially rescued the migration defects caused by loss of YAP and TAZ function. Finally, we found that cytoplasmic YAP positively regulated the activity of the small GTPase CDC42, deletion of which caused severe defects in endothelial migration. These findings uncover a previously unrecognized role of cytoplasmic YAP/TAZ in promoting cell migration by activating CDC42 and provide insight into how Hippo signaling in ECs regulates angiogenesis.

中文翻译：

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YAP/TAZ-CDC42 信号调节血管尖端细胞迁移

血管生成和血管重塑对于器官生成过程中血管网络的建立至关重要。在这里，我们表明，在视网膜血管生成过程中，血管内皮细胞 (EC) 的增殖和迁移需要 Hippo 信号通路效应子 YAP 和 TAZ，以基因剂量依赖性方式。有趣的是，由Lats1 / 2缺失诱导的 YAP 和 TAZ 的核易位阻止了内皮迁移和表型复制的Yap/Taz- 缺乏突变体。此外，细胞质形式的 YAP (YAPS127D) 的过度表达部分挽救了由 YAP 和 TAZ 功能丧失引起的迁移缺陷。最后，我们发现细胞质 YAP 正调节小 GTPase CDC42 的活性，其缺失导致内皮迁移的严重缺陷。这些发现揭示了细胞质 YAP/TAZ 在通过激活 CDC42 促进细胞迁移方面的先前未被认识的作用，并提供了对 EC 中 Hippo 信号传导如何调节血管生成的见解。