NOGO-A induction and localization during chick brain development indicate a role disparate from neurite outgrowth inhibition.
BACKGROUND
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.


RESULTS
We isolated chicken NOGO-A 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. NOGO gene transcripts (NOGO-A, NOGO-B and NOGO-C) were differentially expressed in the CNS during development and a second NOGO-A splice variant was identified. We further localized NOGO-A expression during key phases of CNS development by in situ hybridization. CNS-associated NOGO-A 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.


CONCLUSIONS
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.
Caltharp
Shelley A
SA
Department of Pathology and Human Anatomy, Division of Human Anatomy, Loma Linda University and Medical Center, Loma Linda, CA 92350, USA. scaltharp@llu.edu <scaltharp@llu.edu>
Pira
Charmaine U
CU
Mishima
Noboru
N
Youngdale
Erik N
EN
McNeill
David S
DS
Liwnicz
Boleslaw H
BH
Oberg
Kerby C
KC
D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D001921:Brain / Q000196:embryology* / Q000378:metabolism; D002642:Chick Embryo; D017124:Conserved Sequence; D019143:Evolution, Molecular; D051519:Fibroblast Growth Factor 4 / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D008954:Models, Biological; D008969:Molecular Sequence Data; D009185:Myelin Proteins / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism* / Q000502:physiology*; D016501:Neurites / Q000378:metabolism*; D000070798:Nogo Proteins; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
D051519:Fibroblast Growth Factor 4; D009185:Myelin Proteins; D000070798:Nogo Proteins; C000603199:RTN4 protein, human