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 bothin vitroexperiments andin vivopharmacological 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 homozygousnogo-ab^trap/trapmice, but not innogo-ab^atg/atgmice. CST regeneration is also present after pharmacological NgR blockade, but not inngr1^−/−mice. To assess thenogo-ab^atgandngr1-null alleles for other axon growth phenotypes, we created unilateral pyramidotomies and monitored the uninjured CST. There is robust pyramidotomy-induced growth ofnogo-ab^atg/atgandngr1^−/−CST axons into denervated cervical gray matter. This fiber growth correlates with recovery of fine motor skill in the affected forelimb. Thusnogo-abandngr1play a modulated role in limiting CNS axonal growth across a spectrum of different tracts in various lesion models.