Nrarp Coordinates Endothelial Notch and Wnt Signaling to Control Vessel Density in Angiogenesis
| Autor: | Li-Kun Phng, Sujata Rao, Richard A. Lang, Ivan B. Lobov, Michael Potente, Jennifer K. Ondr, Daniel Nyqvist, Jonathan D. Leslie, Gavin Thurston, Jane Babbage, Holger Gerhardt |
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| Rok vydání: | 2009 |
| Předmět: |
medicine.medical_specialty
Cell signaling Sialomucins Endothelium Lymphoid Enhancer-Binding Factor 1 Angiogenesis Notch signaling pathway Neovascularization Physiologic DEVBIO Biology Article Retina General Biochemistry Genetics and Molecular Biology Mice Internal medicine Morphogenesis medicine Animals RNA Small Interfering Molecular Biology Zebrafish beta Catenin Receptors Notch Intracellular Signaling Peptides and Proteins Wnt signaling pathway Endothelial Cells Proteins Cell Biology Zebrafish Proteins biology.organism_classification Cell biology Wnt Proteins medicine.anatomical_structure Endocrinology cardiovascular system Blood Vessels Female Signal transduction WNT3A Signal Transduction Transcription Factors Developmental Biology |
| Zdroj: | Dev Cell |
| ISSN: | 1534-5807 |
| Popis: | SummaryWhen and where to make or break new blood vessel connections is the key to understanding guided vascular patterning. VEGF-A stimulation and Dll4/Notch signaling cooperatively control the number of new connections by regulating endothelial tip cell formation. Here, we show that the Notch-regulated ankyrin repeat protein (Nrarp) acts as a molecular link between Notch- and Lef1-dependent Wnt signaling in endothelial cells to control stability of new vessel connections in mouse and zebrafish. Dll4/Notch-induced expression of Nrarp limits Notch signaling and promotes Wnt/Ctnnb1 signaling in endothelial stalk cells through interactions with Lef1. BATgal-reporter expression confirms Wnt signaling activity in endothelial stalk cells. Ex vivo, combined Wnt3a and Dll4 stimulation of endothelial cells enhances Wnt-reporter activity, which is abrogated by loss of Nrarp. In vivo, loss of Nrarp, Lef1, or endothelial Ctnnb1 causes vessel regression. We suggest that the balance between Notch and Wnt signaling determines whether to make or break new vessel connections. |
| Databáze: | OpenAIRE |
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