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Circulation Research. 2003;92:300-307
Published online before print January 2, 2003, doi: 10.1161/01.RES.0000055016.36679.23
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(Circulation Research. 2003;92:300.)
© 2003 American Heart Association, Inc.

Integrative Physiology

Focal Adhesion Kinase Is Required for Blood Vessel Morphogenesis

Dusko Ilic, Branka Kovacic, Susan McDonagh, Fang Jin, Clark Baumbusch, David G. Gardner, Caroline H. Damsky

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.

Correspondence to Dusko Ilic, Department of Stomatology, UCSF, 513 Parnassus, S-501, San Francisco, CA 94143-0512. 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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