Summary: | <p>Abstract</p> <p>Background</p> <p>Nogo-A, a myelin-associated protein, inhibits neurite outgrowth and abates regeneration in the adult vertebrate central nervous system (CNS) and may play a role in maintaining neural pathways once established. However, the presence of Nogo-A during early CNS development is counterintuitive and hints at an additional role for Nogo-A beyond neurite inhibition.</p> <p>Results</p> <p>We isolated chicken <it>NOGO-A </it>and determined its sequence. A multiple alignment of the amino acid sequence across divergent species, identified five previously undescribed, Nogo-A specific conserved regions that may be relevant for development. <it>NOGO </it>gene transcripts (<it>NOGO-A</it>, <it>NOGO-B </it>and <it>NOGO-C</it>) were differentially expressed in the CNS during development and a second <it>NOGO-A </it>splice variant was identified. We further localized NOGO-A expression during key phases of CNS development by <it>in situ </it>hybridization. CNS-associated <it>NOGO-A </it>was induced coincident with neural plate formation and up-regulated by FGF in the transformation of non-neural ectoderm into neural precursors. NOGO-A expression was diffuse in the neuroectoderm during the early proliferative phase of development, and migration, but localized to large projection neurons of the optic tectum and tectal-associated nuclei during architectural differentiation, lamination and network establishment.</p> <p>Conclusion</p> <p>These data suggest Nogo-A plays a functional 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. These data indicate that Nogo-A is a multifunctional protein with additional roles during CNS development that are disparate from its later role of neurite outgrowth inhibition in the adult CNS.</p>
|