Ephrin-B2 controls cell motility and adhesion during blood-vessel-wall assembly.
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.
Foo
Shane S
SS
Vascular Development Laboratory, Cancer Research UK London Research Institute, London WC2A 3PX, UK.
Turner
Christopher J
CJ
Adams
Susanne
S
Compagni
Amelia
A
Aubyn
Deborah
D
Kogata
Naoko
N
Lindblom
Per
P
Shani
Moshe
M
Zicha
Daniel
D
Adams
Ralf H
RH
D000818:Animals; D001808:Blood Vessels / Q000166:cytology / Q000187:drug effects / Q000254:growth & development*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D036388:Ephrin-B2 / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D018919:Neovascularization, Physiologic / Q000502:physiology; D010641:Phenotype; D015398:Signal Transduction / Q000502:physiology
D036388:Ephrin-B2