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ZIRC
ZFIN ID: ZDB-PUB-111027-31
Rspo1/Wnt signaling promotes angiogenesis via Vegfc/Vegfr3
Gore, A.V., Swift, M.R., Cha, Y.R., Lo, B., McKinney, M.C., Li, W., Castranova, D., Davis, A., Mukouyama, Y.S., and Weinstein, B.M.
Date: 2011
Source: Development (Cambridge, England) 138(22): 4875-4886 (Journal)
Registered Authors: Castranova, Dan, Cha, Young, Davis, Andrew, Gore, Aniket, Lo, Brigid, Swift, Matthew Russell, Weinstein, Brant M.
Keywords: angiogenesis, Vegfc, zebrafish
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Cells, Cultured
  • Embryo, Nonmammalian
  • Gene Expression Regulation, Developmental
  • Models, Biological
  • Neovascularization, Pathologic/genetics
  • Neovascularization, Pathologic/metabolism
  • Neovascularization, Physiologic/genetics*
  • Up-Regulation/genetics
  • Up-Regulation/physiology
  • Vascular Endothelial Growth Factor C/genetics
  • Vascular Endothelial Growth Factor C/metabolism
  • Vascular Endothelial Growth Factor C/physiology*
  • Vascular Endothelial Growth Factor Receptor-3/genetics
  • Vascular Endothelial Growth Factor Receptor-3/metabolism
  • Vascular Endothelial Growth Factor Receptor-3/physiology*
  • Wnt Proteins/genetics
  • Wnt Proteins/metabolism
  • Wnt Signaling Pathway/genetics
  • Wnt Signaling Pathway/physiology*
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/physiology
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • Zebrafish Proteins/physiology*
PubMed: 22007135 Full text @ Development
FIGURES
ABSTRACT

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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