EphA4 regulates central nervous system vascular formation
EphA4 regulates central nervous system vascular formation
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DOI：
10.1002/cne.21029
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发表时间：
2006-08-20
影响因子：
2.5
通讯作者：
Turnley, Ann M.
中科院分区：
文献类型：
--
作者：
Goldshmit, Yona;Galea, Mary P.;Turnley, Ann M.
参与轴突引导的分子最近也被证明在血管引导中发挥作用。为了检查轴突引导分子，如EphA 4受体酪氨酸激酶，是否也可能在中枢神经系统（CNS）脉管系统的发育和CNS损伤后的修复中发挥作用，我们检查了野生型和EphA 4无效突变（-/-）小鼠。EphA 4-/-小鼠的大脑皮质和脊髓中都表现出异常的中枢神经系统血管结构，分支混乱，直径小30%。在发育过程中，EphA 4在内皮细胞上表达。这种表达模式在成年人中没有保持。野生型小鼠脊髓损伤后，EphA 4的表达在活化的星形胶质细胞上显著上调，其中许多与血管密切相关。在损伤后的EphA 4-/-脊髓中，星形胶质细胞与血管的联系不如野生型星形胶质细胞紧密。在未受伤的EphA 4-/-小鼠中，血脑屏障（BBB）似乎正常，但在脊髓损伤后显示出长时间的渗漏。这些结果支持EphA 4在发育期间在CNS血管形成和引导中的作用以及在BBB修复中的额外作用。
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.