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Published 3 January 2006. doi:10.1083/jcb.200506184
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 172, Number 1, 151-162
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Article

Endothelial FAK is essential for vascular network stability, cell survival, and lamellipodial formation



Rickmer Braren1, Huiqing Hu1, Yung Hae Kim1, Hilary E. Beggs2,3, Louis F. Reichardt2, and Rong Wang1

1 The Pacific Vascular Research Laboratory, Division of Vascular Surgery, Department of Surgery
2 Program in Neuroscience, Department of Physiology, Howard Hughes Medical Institute
3 Department of Ophthalmology, University of California, San Francisco, San Francisco, CA 94143

Correspondence to Rong Wang: wangr{at}surgery.ucsf.edu

Morphogenesis of a vascular network requires dynamic vessel growth and regression. To investigate the cellular mechanism underlying this process, we deleted focal adhesion kinase (FAK), a key signaling mediator, in endothelial cells (ECs) using Tie2-Cre mice. Targeted FAK depletion occurred efficiently early in development, where mutants exhibited a distinctive and irregular vasculature, resulting in hemorrhage and lethality between embryonic day (e) 10.5 and 11.5. Capillaries and intercapillary spaces in yolk sacs were dilated before any other detectable abnormalities at e9.5, and explants demonstrate that the defects resulted from the loss of FAK and not from organ failure. Time-lapse microscopy monitoring EC behavior during vascular formation in explants revealed no apparent decrease in proliferation or migration but revealed increases in cell retraction and death leading to reduced vessel growth and increased vessel regression. Consistent with this phenotype, ECs derived from mutant embryos exhibited aberrant lamellipodial extensions, altered actin cytoskeleton, and nonpolarized cell movement. This study reveals that FAK is crucial for vascular morphogenesis and the regulation of EC survival and morphology.

R. Braren and H. Hu contributed equally to this paper.

R. Braren's present address is Department for Diagnostic Radiology, Technical University Munich, Munich 80290, Germany.

Abbreviations used in this paper: Ab, antibody; EC, endothelial cell; FN, fibronectin; FRNK, FAK-related nonkinase; IP, immunoprecipitation; LM, laminin; NE, neuroepithelium; o/n, overnight; PLL, poly-L-lysine; P-Sp, para-aortic splanchnopleural mesoderm; SM{alpha}A, smooth muscle {alpha}-actin; Tg, transgenic; YS, yolk sac.


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