Published online before print January 2, 2003, doi: 10.1161/01.RES.0000055016.36679.23
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Submitted on July 24, 2001
Revised on December 20, 2002
Accepted on December 20, 2002
Focal Adhesion Kinase Is Required for Blood Vessel Morphogenesis
Dusko Ilic *;
From the Departments of Stomatology (D.I., S.M., C.B., C.H.D.), Medicine (B.K., D.G.G.), and Anatomy (C.H.D.), University of California San Francisco (UCSF), San Francisco, Calif; and Berlex Biosciences (F.J.), Gene Therapy Department, Richmond, Calif.
* To whom correspondence should be addressed. E-mail: ilic{at}itsa.ucsf.edu.
The nonreceptor tyrosine kinase focal adhesion kinase (FAK) is a point of convergence for signals from extracellular matrix, soluble factors, and mechanical stimuli. Targeted disruption of the fak gene in mice leads to death at embryonic day 8.5 (E8.5). FAK-/- embryos have severely impaired blood vessel development. Gene expression and in vitro differentiation studies revealed that endothelial cell differentiation was comparable in FAK-/- and wild-type E8.5 embryos. We examined the role of FAK in blood vessel morphogenesis using an in vitro tubulogenesis assay and three different culture systems: FAK+/+ and FAK-/- embryoid bodies, FAK+/+ and FAK-/- endothelial cells, and human umbilical vein endothelial cells expressing antisense FAK, a dominant-negative fragment of FAK, or wild-type FAK. In all of these systems, endothelial cells deficient in FAK expression or function displayed a severely reduced ability to form tubules in Matrigel. These studies demonstrate clearly that the vascular defects in FAK-/- mice result from the inability of FAK-deficient endothelial cells to organize themselves into vascular networks, rather than from defects in tissue-specific differentiation.
Key words: focal adhesion kinase • vasculogenesis • angiogenesis • fibronectin • endothelial cell differentiation
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