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Development 2008 Nov 01;13522:3655-64. doi: 10.1242/dev.027284.
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The Wnt signaling regulator R-spondin 3 promotes angioblast and vascular development.

Kazanskaya O , Ohkawara B , Heroult M , Wu W , Maltry N , Augustin HG , Niehrs C .

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.

PubMed ID: 18842812
Article link: Development

Species referenced: Xenopus laevis
Genes referenced: aplnr dkk1 hba1 kdr pecam1 rspo2 rspo3 sacs tal1 tcf7l1 vegfa wnt3a wnt8a
Morpholinos: rspo3 MO1 vegfa MO1

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