Shifman M I, Selzer M E
Department of Neurology, University of Pennsylvania Medical Center, Philadelphia, PA 19104-4283, USA.
Neurorehabil Neural Repair. 2000;14(1):49-58. doi: 10.1177/154596830001400106.
The sea lamprey recovers from spinal cord transection by a process that involves directionally specific regeneration of axons. The mechanisms underlying this specificity are not known, but they may involve molecular cues similar to those that guide the growth of spinal cord axons during development, such as netrins and semaphorins. To test the role of guidance cues in regeneration, we cloned netrin and its receptor UNC-5 from lamprey central nervous system (CNS) and studied their expression after spinal cord transection. In situ hybridization showed that (1) mRNA for netrin is expressed in the spinal cord, primarily in neurons of the lateral gray matter and in dorsal cells; (2) mRNA for UNC-5 is expressed in lamprey reticulospinal neurons; (3) following spinal cord transection, UNC-5 message was dramatically downregulated at two weeks, during the period of axon dieback; (4) UNC-5 message was upregulated at three weeks, when many axons are beginning to regenerate; and (5) axotomy-induced expression of UNC-5 occurred primarily in neurons whose axons regenerate poorly. Because the UNC-5 receptor is thought to mediate the chemorepellent effects of netrins, netrin signaling may play a role in limiting or channeling the regeneration of certain neurons. These data strengthen the rationale for studying the role of developmental guidance molecules in CNS regeneration.
七鳃鳗可通过一个涉及轴突定向特异性再生的过程从脊髓横断损伤中恢复。这种特异性背后的机制尚不清楚，但可能涉及与发育过程中引导脊髓轴突生长的分子信号类似的分子信号，如网蛋白和信号素。为了测试引导信号在再生中的作用，我们从七鳃鳗中枢神经系统（CNS）中克隆了网蛋白及其受体UNC-5，并研究了脊髓横断损伤后它们的表达情况。原位杂交显示：（1）网蛋白的mRNA在脊髓中表达，主要在外侧灰质神经元和背侧细胞中表达；（2）UNC-5的mRNA在七鳃鳗网状脊髓神经元中表达；（3）脊髓横断损伤后，在轴突回缩期的两周时，UNC-5的信息显著下调；（4）在三周时，当许多轴突开始再生时，UNC-5的信息上调；（5）轴突切断诱导的UNC-5表达主要发生在轴突再生较差的神经元中。由于UNC-5受体被认为介导网蛋白的化学排斥作用，网蛋白信号传导可能在限制或引导某些神经元的再生中发挥作用。这些数据强化了研究发育引导分子在中枢神经系统再生中作用的理论依据。
