Identification of two NOGO/RTN4 genes and analysis of Nogo-A expression in Xenopus laevis.

Myelin-associated axon growth inhibitors such as Nogo-A/RTN4-A impair axon regeneration in the adult mammalian central nervous system (CNS). Here, we describe the cloning and expression of two independent Xenopus laevis rtn4 orthologs. As in mammals, alternative transcripts are generated both through differential splicing and promoter usage, giving rise to Xenopus nogo-A, -B, -C and to a new isoform, nogo-N/rtn4-N. Xenopus is therefore the 'lowest' vertebrate where Nogo-A was identified. Xenopus Nogo-A/RTN4-A is predominantly expressed in the nervous system, whereas the other isoforms mainly occur in nonneuronal tissues. Nogo-A/RTN4-A specific antisera detect the protein in myelinated fiber tracts of the spinal cord, hindbrain, optic nerve, tectum opticum and in isolated oligodendrocytes. In addition, subpopulations of CNS neurons are Nogo-A/RTN4-A positive. This expression pattern is consistent with that observed for rat Nogo-A and suggests similar functions. Nogo-A in Xenopus myelin might therefore contribute to the failure of spinal cord regeneration in frogs-a feature that may have evolved during the transition from fish to land vertebrates.