The natural history of the myelin-derived nerve growth inhibitor Nogo-A

Nogo-A is possibly the best characterized myelin-derived inhibitor of nerve growth in the adult central nervous system (CNS). It is a member of the ancient reticulon family of mainly endoplasmic reticulum resident proteins with representatives found throughout the eukaryotic domain. Orthologs of the nogo gene were identified in tetrapods and teleost fish but none have been detected in invertebrates. Evolution of the nogo gene has been non-homogeneous. The exon–intron arrangement is conserved from amphibians (Xenopus) to mammals, but partly deviates from that found in several teleost fish species, indicating that the recruitment of nogo exons proceeded along at least two independent lines during early vertebrate evolution. This might have far-reaching consequences. Tetrapod nogo orthologs encode two neurite growth inhibitory domains whereas in fish nogo only one of the inhibitory domains is present. These distinct paths in nogo evolution have potentially contributed to the regeneration permissive CNS in fish as opposed to the non-regenerating CNS in higher vertebrates.