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A more recent version of this article appeared on July 1, 2002
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Submitted on January 7, 2001
Revised on March 27, 2002
Accepted on April 5, 2002
1 MRC Laboratory for Molecular Cell Biology, CRC Oncogene and Signal Transduction Group and Department of Medicine, University College London, London WC1E 6BT, United Kingdom
2 MRC Laboratory for Molecular Cell Biology, CRC Oncogene and Signal Transduction Group, University College London, London WC1E 6BT, United Kingdom
3 MRC Laboratory for Molecular Cell Biology, CRC Oncogene and Signal Transduction Group and Department of Biochemistry, University College London, London WC1E 6BT, United Kingdom
* Corresponding author. E-mail address: J.Connolly{at}ucl.ac.uk.
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. 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. Inhibition of microtubule dynamics however, 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, while Pak, 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.
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