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EphA4 regulates central nervous system vascular formation
Author(s) -
Goldshmit Yona,
Galea Mary P.,
Bartlett Perry F.,
Turnley Ann M.
Publication year - 2006
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.21029
Subject(s) - biology , central nervous system , neuroscience , nervous system , anatomy
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. J. Comp. Neurol. 497:864–875, 2006. © 2006 Wiley‐Liss, Inc.