JCB logo
PeproTech: Your source for Cell Biology Research Reagents
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 3 January 2006. doi:10.1083/jcb.200506184
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 172, Number 1, 151-162
This Article
Right arrow Full Text
Right arrow PDF (Full Text)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Braren, R.
Right arrow Articles by Wang, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Braren, R.
Right arrow Articles by Wang, R.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

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.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents