The Nogo-Nogo receptor pathway limits a spectrum of adult CNS axonal growth

Abstract

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-abtrap/trap mice, but not in nogo-abatg/atg mice. CST regeneration is also present after pharmacological NgR blockade, but not in ngr1-/- mice. To assess the nogo-abatg 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-abatg/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. Copyright © 2006 Society for Neuroscience.