Development (Cambridge), 2011-11, Vol.138 (22), p.4875-4886
2011
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- Rspo1/Wnt signaling promotes angiogenesis via Vegfc/Vegfr3
- Ist Teil von
- Development (Cambridge), 2011-11, Vol.138 (22), p.4875-4886
- Ort / Verlag
- England: Company of Biologists
- Erscheinungsjahr
- 2011
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0950-1991eISSN: 1477-9129DOI: 10.1242/dev.068460Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3201658
- Format
- –
- Schlagworte
- Animals, Animals, Genetically Modified, Cells, Cultured, Danio rerio, 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