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Vol. 13, Issue 7, 2474-2485, July 2002
*Medical Research Council Laboratory for Molecular Cell
Biology, Endothelial cells undergo branching morphogenesis to form capillary
tubes. We have utilized an in vitro Matrigel overlay assay to analyze
the role of the cytoskeleton and Rho GTPases during this process. The
addition of matrix first induces changes in cell morphology
characterized by the formation of dynamic cellular protrusions and the
assembly of discrete aggregates or cords of aligned cells resembling
primitive capillary-like structures, but without a recognizable lumen.
This is followed by cell migration leading to the formation of a
complex interconnecting network of capillary tubes with readily
identifiable lumens. Inhibition of actin polymerization or actin-myosin
contraction inhibits cell migration but has no effect on the initial
changes in endothelial cell morphology. However, inhibition of
microtubule dynamics prevents both the initial cell shape changes as
well as cell migration. We find that the small GTPase Rac is essential
for the matrix-induced changes in endothelial cell morphology, whereas
p21-activated kinase, an effector of Rac, is required for cell
motility. We conclude that Rac integrates signaling through both the
actin and microtubule cytoskeletons to promote capillary tube assembly.
Cancer Research Campaign Oncogene and
Signal Transduction Group, and Departments of Medicine
and §Biochemistry, University College London, London WC1E
6BT, United Kingdom
Corresponding author. E-mail address:
J.Connolly{at}ucl.ac.uk.
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