Nogo-A in the oligodendrocytes/CNS myelin membrane potently inhibits CNS axon regeneration in mammals. Nogo-A is the largest of the three Reticulon-4 (RTN-4)/nogo gene transcripts (-A, -B, -C) which share the evolutionarily conserved C-terminal common region (CR). In mammals, growth inhibition is exerted by the Nogo-A specific N-terminal domain via one type of receptor (see TP C1), and seemingly also by the Nogo-66 loop of the CR domain via the "Nogo-66 Receptor" (NgR). It is unclear how Nogo-A reaches the plasma membrane and whether it can acquire two orientations.pbr Inhibition by oligodendrocytes/myelin membrane proteins does not occur in the fish CNS or in the frog optic nerve where axons regenerate but is observed in the frog spinal cord. Thus, we cloned RTN-4/nogo transcripts in Xenopus and zebrafish. We identified duplicated Xenopus Nogo-A, -B, -C homologs and showed the presence of Nogo-A1/-A2 in CNS myelin. Distribution, surface expression and function is now being characterized in co-cultures of oligodendrocytes and axons, with antibodies against the Nogo-A specific and Nogo-66 domains (CR), respectively.pbr No Nogo-A homologs were found so far in fish but three RTN-4 gene transcripts (α, β,γ) with CR (Nogo-66) domain are present. The fish RTN-4 N-termini, however, markedly differ from land vertebrate RTN-4/nogo gene transcripts. Still, fish axons are inhibited by mammalian CNS myelin which speaks for the presence of receptors and functions of Nogo homologues. We will analyze expression patterns and functions of fish RTN-4/nogo gene transcripts, of the Nogo-66 domain and the cloned receptor homologs (NgR for Nogo-66) and search for the Nogo-A specific receptor (in coop. with TP C1).
