Involvement of the myelin-associated inhibitor Nogo-A in early cortical development and neuronal maturation.
Nogo-A is a myelin-associated protein expressed by neurons and myelinating mature oligodendrocytes in the central nervous system. Although most research has focused on the participation of Nogo-A in the prevention of axonal regeneration and plasticity in the adult, little attention has been paid to the putative functions of Nogo-A during embryonic development. Here we examined the general pattern and cell-specific distribution of Nogo-A in the prenatal mouse telencephalon. In addition, we studied the development of the major axon tracts and radial and tangential migration in Nogo-A/B/C knockout mice. The pattern of Nogo-A showed distinct distribution in radial glia and postmitotic neurons, in which it is particularly enriched in developing axons. Similarly, Nogo-A was enriched at the leading process of tangentially migrating interneurons but not detectable in radial migrating neurons. Although a low level of Nogo-A appears to be on the surface of many cortical neurons, most proteins have intracellular localization. In Nogo-deficient background, neurons displayed early polarization and increased branching in vitro, probably reflecting a cell-intrinsic role of Nogo proteins in branching reduction, and early tangential migration was delayed. On the basis of these observations, we propose that Nogo proteins, particularly Nogo-A, are involved in multiple processes during cortical development.
Mingorance-Le Meur
Ana
A
Department of Cell Biology, Cellular and Molecular Basis of Neurodegeneration and Neurorepair, Institute for Research in Biomedicine, University of Barcelona, Barcelona Science Park, Josep Samitier 1-5, 08028 Barcelona, Spain. alemeur@interchange.ubc.ca
Zheng
Binhai
B
Soriano
Eduardo
E
del Río
José A
JA
D000375:Aging; D000818:Animals; D001369:Axons / Q000502:physiology*; D001931:Brain Mapping; D002465:Cell Movement; D002540:Cerebral Cortex / Q000196:embryology* / Q000254:growth & development / Q000502:physiology*; D003599:Cytoskeleton / Q000502:physiology; D005333:Fetus; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009185:Myelin Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009416:Nerve Regeneration / Q000502:physiology; D016501:Neurites / Q000648:ultrastructure; D009474:Neurons / Q000502:physiology*; D000070798:Nogo Proteins; D013687:Telencephalon / Q000196:embryology / Q000201:enzymology / Q000502:physiology
D009185:Myelin Proteins; D000070798:Nogo Proteins; C000603201:Rtn4 protein, mouse