Rspo1/Wnt signaling promotes angiogenesis via Vegfc/Vegfr3.

Research paper by Aniket V AV Gore, Matthew R MR Swift, Young R YR Cha, Brigid B Lo, Mary C MC McKinney, Wenling W Li, Daniel D Castranova, Andrew A Davis, Yoh-suke YS Mukouyama, Brant M BM Weinstein

Indexed on: 19 Oct '11Published on: 19 Oct '11Published in: Development (Cambridge, England)


Here, we show that a novel Rspo1-Wnt-Vegfc-Vegfr3 signaling pathway plays an essential role in developmental angiogenesis. A mutation in R-spondin1 (rspo1), a Wnt signaling regulator, was uncovered during a forward-genetic screen for angiogenesis-deficient mutants in the zebrafish. Embryos lacking rspo1 or the proposed rspo1 receptor kremen form primary vessels by vasculogenesis, but are defective in subsequent angiogenesis. Endothelial cell-autonomous inhibition of canonical Wnt signaling also blocks angiogenesis in vivo. The pro-angiogenic effects of Rspo1/Wnt signaling are mediated by Vegfc/Vegfr3(Flt4) signaling. Vegfc expression is dependent on Rspo1 and Wnt, and Vegfc and Vegfr3 are necessary to promote angiogenesis downstream from Rspo1-Wnt. As all of these molecules are expressed by the endothelium during sprouting stages, these results suggest that Rspo1-Wnt-VegfC-Vegfr3 signaling plays a crucial role as an endothelial-autonomous permissive cue for developmental angiogenesis.

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