Research article

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

Shelley A Caltharp¹ , Charmaine U Pira¹ , Noboru Mishima¹ , Erik N Youngdale¹ , David S McNeill¹ , Boleslaw H Liwnicz¹ and Kerby C Oberg^1,2

¹  Department of Pathology and Human Anatomy, Division of Human Anatomy, Loma Linda University and Medical Center, Loma Linda, CA 92350, USA

²  Department of Surgery, Division of Plastic and Reconstructive Surgery, Loma Linda University and Medical Center, Loma Linda, CA 92350, USA

author email corresponding author email

BMC Developmental Biology 2007, 7:32doi:10.1186/1471-213X-7-32

Published:	14 April 2007

Abstract

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.

Conclusion

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.