Co-Authors:
Foo, S.S., Vascular Development Laboratory, Cancer Research UK London Research Institute, London WC2A 3PX, United Kingdom, Cancer Research Technology, London WC1E 6BT, United Kingdom
Turner, C.J., Vascular Development Laboratory, Cancer Research UK London Research Institute, London WC2A 3PX, United Kingdom
Adams, S., Vascular Development Laboratory, Cancer Research UK London Research Institute, London WC2A 3PX, United Kingdom
Compagni, A., Vascular Development Laboratory, Cancer Research UK London Research Institute, London WC2A 3PX, United Kingdom, Bocconi University, 20136 Milan, Italy
Aubyn, D., Light Microscopy Laboratory, Cancer Research UK London Research Institute, London WC2A 3PX, United Kingdom
Kogata, N., Vascular Development Laboratory, Cancer Research UK London Research Institute, London WC2A 3PX, United Kingdom
Lindblom, P., Vascular Development Laboratory, Cancer Research UK London Research Institute, London WC2A 3PX, United Kingdom, Vascular Biology Laboratory, Cancer Research UK London Research Institute, London WC2A 3PX, United Kingdom
Shani, M., Institute of Animal Science, Volcani Center, Bet Dagan 50250, Israel
Zicha, D., Light Microscopy Laboratory, Cancer Research UK London Research Institute, London WC2A 3PX, United Kingdom
Adams, R.H., Vascular Development Laboratory, Cancer Research UK London Research Institute, London WC2A 3PX, United Kingdom
Abstract:
New blood vessels are initially formed through the assembly or sprouting of endothelial cells, but the recruitment of supporting pericytes and vascular smooth muscle cells (mural cells) ensures the formation of a mature and stable vascular network. Defective mural-cell coverage is associated with the poorly organized and leaky vasculature seen in tumors or other human diseases. Here we report that mural cells require ephrin-B2, a ligand for Eph receptor tyrosine kinases, for normal association with small-diameter blood vessels (microvessels). Tissue-specific mutant mice display perinatal lethality; vascular defects in skin, lung, gastrointestinal tract, and kidney glomeruli; and abnormal migration of smooth muscle cells to lymphatic capillaries. Cultured ephrin-B2-deficient smooth muscle cells are defective in spreading, focal-adhesion formation, and polarized migration and show increased motility. Our results indicate that the role of ephrin-B2 and EphB receptors in these processes involves Crk-p130(CAS) signaling and suggest that ephrin-B2 has some cell-cell-contact-independent functions. ©2006 Elsevier Inc.
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