Endothelial cell talin1 is essential for embryonic angiogenesis

被引:56
|
作者
Monkley, Susan J. [1 ]
Kostourou, Vassiliki [2 ]
Spence, Lorraine [1 ]
Petrich, Brian [3 ]
Coleman, Stacey [1 ]
Ginsberg, Mark H. [3 ]
Pritchard, Catrin A. [1 ]
Critchley, David R. [1 ]
机构
[1] Univ Leicester, Dept Biochem, Leicester LE1 9HN, Leics, England
[2] BSRC Al Fleming, Vasc Adhes Lab, Athens, Greece
[3] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA
基金
英国惠康基金;
关键词
Angiogenesis; Cell adhesion; Endothelial cells; Talin1; Talin2; INTEGRIN ACTIVATION; MOUSE DEVELOPMENT; STRUCTURAL BASIS; BINDING-SITES; DOMAIN; BETA-1-INTEGRIN; EXPRESSION; REVEALS; COMPLEX; MICE;
D O I
10.1016/j.ydbio.2010.11.010
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Using Tln1(ft/ft);CreER mice, we show that tamoxifen-induced inactivation of the talin1 gene throughout the embryo produces an angiogenesis phenotype that is restricted to newly forming blood vessels. The phenotype has a rapid onset in early embryos, resulting in vessel defects by 48 h and death of the embryo within 72 h. Very similar vascular defects were obtained using a Tie2-Cre endothelial cell-specific Tln1 knockout, a phenotype that was rescued by expression of a Tln1 mini-gene in endothelial cells. We show that endothelial cells, unlike most other cell types, do not express talin2, which can compensate for loss of talin1, and demonstrate for the first time that endothelial cells in vivo lacking talin1 are unable to undergo the cell spreading and flattening required to form vessels. (C) 2010 Elsevier Inc. All rights reserved.
引用
收藏
页码:494 / 502
页数:9
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