EphA4 regulates central nervous system vascular formation.
Molecules involved in axon guidance have recently also been shown to play a role in blood vessel guidance. To examine whether axon guidance molecules, such as the EphA4 receptor tyrosine kinase, might also play a role in development of the central nervous system (CNS) vasculature and repair following CNS injury, we examined wild-type and EphA4 null mutant (-/-) mice. EphA4-/- mice exhibited an abnormal CNS vascular structure in both the cerebral cortex and the spinal cord, with disorganized branching and a 30% smaller diameter. During development, EphA4 was expressed on endothelial cells. This pattern of expression was not maintained in the adult. After spinal cord injury in wild-type mice, expression of EphA4 was markedly up-regulated on activated astrocytes, many of which were tightly associated with blood vessels. In EphA4-/- spinal cord following injury, astrocytes were not as tightly associated with blood vessels as the wild-type astrocytes. In uninjured EphA4-/- mice, the blood-brain barrier (BBB) appeared normal, but it showed prolonged leakage following spinal cord injury. These results support a role for EphA4 in CNS vascular formation and guidance during development and an additional role in BBB repair.
Goldshmit
Yona
Y
Centre for Neuroscience, The University of Melbourne, Melbourne, Victoria 3010, Australia.
Galea
Mary P
MP
Bartlett
Perry F
PF
Turnley
Ann M
AM
D000818:Animals; D001812:Blood-Brain Barrier / Q000254:growth & development; D001921:Brain / Q000098:blood supply* / Q000254:growth & development*; D002490:Central Nervous System / Q000098:blood supply / Q000254:growth & development; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D036122:Receptor, EphA4 / Q000172:deficiency / Q000502:physiology*; D013116:Spinal Cord / Q000098:blood supply* / Q000254:growth & development*
D036122:Receptor, EphA4