The Role of Nogo-A During Development of the Chick Central Nervous System

Nogo-A is a potent inhibitor of axon regeneration that is expressed by myelin forming oligodendrocytes of the adult central nervous system (CNS). However, neuronal expression of Nogo-A during development suggests an additional role. Little is known about the putative functions of Nogo-A during embryonic development. To examine its potential role we isolated and analyzed the Nogo-A sequence in the chick, we localized its mRNA expression pattern and cell-specific distribution during key phases of cortical development, and studied regulation of its expression during phases that showed promise of function based on expression patterns. Our results revealed five previously undescribed Nogo-A specific regions from multiple alignment of divergent species. The Nogo gene is differentially expressed during development and we identified a secondary Nogo-A splice variant. In situ hybridization found Nogo-A induction to be coincident with formation of the neural plate, the first visible structure of the CNS. Expression remained diffuse within the neuroepithelia and during later stages of cortical development (proliferation and migration) but showed an increased distribution in large projection neurons during organization of the neuronal network. In addition, we found Nogo-A to be regulated by FGF application, but not by synaptic activity. We identified evolutionarily conserved regulatory sequences surrounding the Nogo gene locus. While they did not appear to play a role in regulating gene expression during early neural development, whether they play a role in later CNS development has yet to be determined. Collectively, these data suggest Nogo-A plays a role in the determination of neural identity and/or differentiation and also appears to play a later role in the networking of large projection neurons during neurite formation and synaptogenesis