期刊
DEVELOPMENTAL CELL
卷 17, 期 4, 页码 505-515出版社
CELL PRESS
DOI: 10.1016/j.devcel.2009.08.011
关键词
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资金
- Deutsche Forschungsgemeinschaft [SFB655]
- Behrens-Weise Foundation
- Heinrich-Heine-University of Dusseldorf
- Ministry of Education, Youth, and Sports of the Czech Republic [MSM 0021620807]
- Heart and Stroke Foundation of British Columbia
- Yukon
- Canadian Institutes for Health Research
In vertebrates, endothelial cells (ECs) form blood vessels in every tissue. Here, we investigated vascular lumen formation in the developing aorta, the first and largest arterial blood vessel in all vertebrates. Comprehensive imaging, pharmacological manipulation, and genetic approaches reveal that, in mouse embryos, the aortic lumen develops extra-cellularly between adjacent ECs. We show that ECs adhere to each other, and that CD34-sialomucins, Moesin, F-actin, and non-muscle Myosin II localize at the endothelial cell-cell contact to define the luminal cell surface. Resultant changes in EC shape lead to lumen formation. Importantly, VE-Cadherin and VEGF-A act at different steps. VE-Cadherin is required for localizing CD34-sialomucins to the endothelial cell-cell contact, a prerequisite to Moesin and F-actin recruitment. In contrast, VEGF-A is required for F-actin-nm-Myosin II interactions and EC shape change. Based on these data, we propose a molecular mechanism of in vivo vascular lumen formation in developing blood vessels.
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