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 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.

Netrin-1 Is a Novel Myelin-Associated Inhibitor to Axon Growth

“…In lamprey, it has also been noted that axonal regeneration capacity inversely correlates with UNC5 receptor expression (Shifman and Selzer, 2000). As noted in the Introduction, attractive or repulsive netrin signaling is mediated by the presence of DCC and UNC5 receptors in neu- insets, c, d).…”

Analysis of 148 kb of Genomic DNA of Tetraodon nigroviridis Covering an Amylase Gene Family*

“…Netrin proteins are guidance molecules, involved either in attracting or repelling the growing axons of a broad range of neuronal cell types during development, and are also involved in controlling neuronal cell migration. The presence of this gene in T. nigroviridis is not surprising, since netrins, as well as their receptors, have been previously identified, even in agnathous fishes (Shimeld 2000;Shifman and Selzer, 2000). A T. nigroviridis assembly sequence presents similarities with the netrin receptor (Fig.…”

Transgenic Zebrafish Lines as Valuable Tools to Understand Successful Spinal Cord Regeneration

“…Lampreys and other species of teleost fishes are being mainly used for this type of studies [lampreys: [5][6][7][8]; teleosts: [9,10]. For example, studies performed using the lamprey model of SCI have shown that different reticulospinal descending neurons projecting in a similar region of the spinal cord have different regenerative abilities after axotomy [4,5] even in the presence of functional recovery. Recent findings using lampreys have also shown that those brain neurons that are "bad regenerators" usually die after a complete spinal cord transaction [3,5].…”

“…In the last decade, zebrafish has appeared as a very valuable genetically tractable model that can be used to understand the mechanisms that control successful spinal cord regeneration in aquatic animals. Lampreys and other species of teleost fishes are being mainly used for this type of studies [lampreys: [5][6][7][8]; teleosts: [9,10]. For example, studies performed using the lamprey model of SCI have shown that different reticulospinal descending neurons projecting in a similar region of the spinal cord have different regenerative abilities after axotomy [4,5] even in the presence of functional recovery.…”

“…For example, studies performed using the lamprey model of SCI have shown that different reticulospinal descending neurons projecting in a similar region of the spinal cord have different regenerative abilities after axotomy [4,5] even in the presence of functional recovery. Recent findings using lampreys have also shown that those brain neurons that are "bad regenerators" usually die after a complete spinal cord transaction [3,5]. Other studies in lampreys have suggested that changes in the expression of axonal guidance molecules or neurotransmitter receptors could be responsible for the success/failure of the regeneration process after injury [11][12][13].…”