The Molecular Basis of Vascular Lumen Formation in the Developing Mouse Aorta

作者：Strilic Boris; Kucera Tomas; Eglinger Jan; Hughes Michael R; McNagny Kelly M; Tsukita Sachiko; Dejana Elisabetta; Ferrara Napoleone; Lammert Eckhard^*

来源：Developmental Cell, 2009, 17(4): 505-515.

DOI：10.1016/j.devcel.2009.08.011

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.

• 出版日期2009-10-20