The Wnt signaling regulator R-spondin 3 promotes angioblast and vascular development
The Wnt signaling regulator R-spondin 3 promotes angioblast and vascular development
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DOI：
10.1242/dev.027284
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发表时间：
2008-11-15
期刊：
影响因子：
4.6
通讯作者：
Niehrs, Christof
中科院分区：
文献类型：
--
作者：
Kazanskaya, Olga;Ohkawara, Bisei;Niehrs, Christof
脊椎动物胚胎血管系统由成血管细胞发育而来，成血管细胞由中胚层前体细胞特化而来，并与血细胞密切相关地发育。调节胚胎血管发生和血管生成的信号尚未完全了解。在此，我们表明R - 脊椎蛋白3（Rspo3），脊椎动物中一个激活Wnt/β - 连环蛋白信号传导的新型分泌蛋白家族的成员，在这些过程中起关键作用。在非洲爪蟾胚胎中，Rspo3的吗啉代反义寡核苷酸敲低会诱导血管缺陷，因为Rspo3对于调节成血管细胞和血细胞特化之间的平衡至关重要。在小鼠中，Rspo3的靶向破坏会导致因血管缺陷引起的胚胎致死。特别是在胎盘中，血管丛的重塑受损。在人内皮细胞中，R - 脊椎蛋白信号传导在体外促进增殖和出芽式血管生成，表明Rspo3可直接调节内皮细胞。我们表明血管内皮生长因子是一个即刻早期反应基因以及R - 脊椎蛋白信号传导的一个介质。这些结果确定Rspo3是胚胎发生过程中一种新型的、在进化上保守的血管生成因子。
The vertebrate embryonic vasculature develops from angioblasts, which are specified from mesodermal precursors and develop in close association with blood cells. The signals that regulate embryonic vasculogenesis and angiogenesis are incompletely understood. Here, we show that R-spondin 3 (Rspo3), a member of a novel family of secreted proteins in vertebrates that activate Wnt/beta-catenin signaling, plays a key role in these processes. In Xenopus embryos, morpholino antisense knockdown of Rspo3 induces vascular defects because Rspo3 is essential for regulating the balance between angioblast and blood cell specification. In mice, targeted disruption of Rspo3 leads to embryonic lethality caused by vascular defects. Specifically in the placenta, remodeling of the vascular plexus is impaired. In human endothelial cells, R-spondin signaling promotes proliferation and sprouting angiogenesis in vitro, indicating that Rspo3 can regulate endothelial cells directly. We show that vascular endothelial growth factor is an immediate early response gene and a mediator of R-spondin signaling. The results identify Rspo3 as a novel, evolutionarily conserved angiogenic factor in embryogenesis.