The Nogo-Nogo receptor pathway limits a spectrum of adult CNS axonal growth.
The hypothesis that Nogo-A (Reticulon 4A) and Nogo-66 receptor (NgR1) limit adult CNS axonal growth after injury is supported by both in vitro experiments and in vivo pharmacological studies. However, genetic assessment of the role of Nogo-A in corticospinal tract (CST) axons after spinal cord dorsal hemisection has yielded conflicting results. CST regeneration is detected in homozygous nogo-ab(trap/trap) mice, but not in nogo-ab(atg/atg) mice. CST regeneration is also present after pharmacological NgR blockade, but not in ngr1(-/-) mice. To assess the nogo-ab(atg) and ngr1-null alleles for other axon growth phenotypes, we created unilateral pyramidotomies and monitored the uninjured CST. There is robust pyramidotomy-induced growth of nogo-ab(atg/atg) and ngr1(-/-) CST axons into denervated cervical gray matter. This fiber growth correlates with recovery of fine motor skill in the affected forelimb. Thus nogo-ab and ngr1 play a modulated role in limiting CNS axonal growth across a spectrum of different tracts in various lesion models.
Cafferty
William B J
WB
Program in Cellular Neuroscience, Neurodegeneration, and Repair, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Strittmatter
Stephen M
SM
D000704:Analysis of Variance; D000818:Animals; D001369:Axons / Q000502:physiology*; D001522:Behavior, Animal; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002490:Central Nervous System / Q000166:cytology*; D007839:Functional Laterality; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D004676:Myelin Basic Protein / Q000378:metabolism; D009185:Myelin Proteins / Q000378:metabolism*; D000070798:Nogo Proteins; D011493:Protein Kinase C / Q000378:metabolism; D011597:Psychomotor Performance / Q000502:physiology; D011712:Pyramidal Tracts / Q000293:injuries / Q000378:metabolism / Q000502:physiology; D018000:Receptors, Peptide / Q000172:deficiency / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D005904:Glial Fibrillary Acidic Protein; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D000070798:Nogo Proteins; D018000:Receptors, Peptide; C000603201:Rtn4 protein, mouse; C087857:protein kinase C gamma; D011493:Protein Kinase C; D015740:Calcitonin Gene-Related Peptide