title: The expression of chemorepulsive guidance receptors and the regenerative abilities of spinal-projecting neurons after spinal cord injury.
abstract: Spinal cord injury (SCI) in mammals leads to permanent loss of function because axons do not regenerate in the central nervous system (CNS). To date, treatments based on neutralizing inhibitory environmental cues, such as the myelin-associated growth inhibitors and chondroitin sulfate proteoglycans, or on adding neurotrophic factors, have had limited success in enhancing regeneration. Published studies suggested that multiple axon guidance cues (repulsive guidance molecule (RGM) family, semaphorins, ephrins, and netrins) persist in adult animals, and that their expression is upregulated after CNS injury. Moreover, many adult CNS neurons continue to express axon guidance receptors. We used the advantages of the lamprey CNS to test the hypotheses that the regenerative abilities of spinal-projecting neurons depend upon their expression of chemorepulsive guidance receptors. After complete spinal transection, lampreys recover behaviorally, and injured axons grow selectively in their correct paths. However, the large identified reticulospinal (RS) neurons in the lamprey brain are heterogeneous in their regenerative abilities - some are high regeneration capacity neurons (probability of axon regeneration >50%), others are low regeneration capacity neurons (<30%). Here we report that the RGM receptor Neogenin is expressed preferentially in the low regeneration capacity RS neurons that regenerate poorly, and that downregulation of Neogenin by morpholino antisense oligonucleotides enhances regeneration of RS axons after SCI. Moreover, lamprey CNS neurons co-express multiple guidance receptors (Neogenin, UNC5 and PlexinA), suggesting that the regenerative abilities of spinal-projecting neurons might reflect the summed influences of the chemorepulsive guidance receptors that they express.
authors.affiliation: Shriners Hospitals Pediatric Research Center (Center for Neural Repair and Rehabilitation), USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Shriners Hospitals Pediatric Research Center (Center for Neural Repair and Rehabilitation), USA.
authors.forename: Cindy
authors.initials: C
authors.lastname: Laramore
authors.affiliation: Shriners Hospitals Pediatric Research Center (Center for Neural Repair and Rehabilitation), USA; Department of Neuroscience, Temple University School of Medicine, 3500 North Broad Street, Philadelphia, PA 19140, USA. Electronic address: mshifman@temple.edu.
authors.forename: Michael I
authors.initials: MI
authors.lastname: Shifman
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D002452:Cell Count; D002633:Chemotaxis / Q000502:physiology*; D004195:Disease Models, Animal; D015536:Down-Regulation; D029941:Fish Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D007798:Lampreys; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D056347:Neuroanatomical Tract-Tracing Techniques; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology; D058630:Spinal Cord Regeneration / Q000502:physiology*
chemical_list: D029941:Fish Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; C091279:neogenin
keywords: Mauthner cell; axon guidance; identifiable neurons; lamprey; mRNA expression; spinal cord regeneration