Expression of the Netrin Receptor UNC-5 in Lamprey Brain: Modulation by Spinal Cord Transection

Abstract

The sea lamprey recovers from spinal cord transection by a process that involves directionally specific regeneration of axons. The mechanisms underlying this speci ficity 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 ex pressed in the spinal cord, primarily in neurons of the lateral gray matter and in dor sal cells; (2) mRNA for UNC-5 is expressed in lamprey reticulospinal neurons; (3) fol lowing 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-in duced expression of UNC-5 occurred primarily in neurons whose axons regenerate poorly. Because the UNC-5 receptor is thought to mediate the chemorepellent ef fects of netrins, netrin signaling may play a role in limiting or channeling the regen eration of certain neurons. These data strengthen the rationale for studying the role of developmental guidance molecules in CNS regeneration.