Tip cell-specific requirement for an atypical Gpr124- and Reck-dependent Wnt/β-catenin pathway during brain angiogenesis
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- Benoit Vanhollebeke
- Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States
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- Oliver A Stone
- Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States
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- Naguissa Bostaille
- Institut de Biologie et de Médecine Moléculaires, Université Libre de Bruxelles, Gosselies, Belgium
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- Chris Cho
- Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, United States
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- Yulian Zhou
- Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, United States
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- Emilie Maquet
- Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States
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- Anne Gauquier
- Institut de Biologie et de Médecine Moléculaires, Université Libre de Bruxelles, Gosselies, Belgium
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- Pauline Cabochette
- Institut de Biologie et de Médecine Moléculaires, Université Libre de Bruxelles, Gosselies, Belgium
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- Shigetomo Fukuhara
- Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan
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- Naoki Mochizuki
- Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan
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- Jeremy Nathans
- Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, United States
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- Didier YR Stainier
- Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States
説明
<jats:p>Despite the critical role of endothelial Wnt/β-catenin signaling during central nervous system (CNS) vascularization, how endothelial cells sense and respond to specific Wnt ligands and what aspects of the multistep process of intra-cerebral blood vessel morphogenesis are controlled by these angiogenic signals remain poorly understood. We addressed these questions at single-cell resolution in zebrafish embryos. We identify the GPI-anchored MMP inhibitor Reck and the adhesion GPCR Gpr124 as integral components of a Wnt7a/Wnt7b-specific signaling complex required for brain angiogenesis and dorsal root ganglia neurogenesis. We further show that this atypical Wnt/β-catenin signaling pathway selectively controls endothelial tip cell function and hence, that mosaic restoration of single wild-type tip cells in Wnt/β-catenin-deficient perineural vessels is sufficient to initiate the formation of CNS vessels. Our results identify molecular determinants of ligand specificity of Wnt/β-catenin signaling and provide evidence for organ-specific control of vascular invasion through tight modulation of tip cell function.</jats:p>
収録刊行物
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- eLife
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eLife 4 e06489-, 2015-06-08
eLife Sciences Publications, Ltd
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詳細情報 詳細情報について
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- CRID
- 1360846646280700672
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- ISSN
- 2050084X
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- 資料種別
- journal article
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- データソース種別
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- Crossref
- KAKEN
