title: Type III neuregulin-1 promotes oligodendrocyte myelination.
abstract: The axonal signals that regulate oligodendrocyte myelination during development of the central nervous system (CNS) have not been established. In this study, we have examined the regulation of oligodendrocyte myelination by the type III isoform of neuregulin-1 (NRG1), a neuronal signal essential for Schwann cell differentiation and myelination. In contrast to Schwann cells, primary oligodendrocytes differentiate normally when cocultured with dorsal root ganglia (DRG) neurons deficient in type III NRG1. However, they myelinate type III NRG1-deficient neurites poorly in comparison to wild type cultures. Type III NRG1 is not sufficient to drive oligodendrocyte myelination as sympathetic neurons are not myelinated even with lentiviral-mediated expression of NRG1. Mice haploinsufficient for type III NRG1 are hypomyelinated in the brain, as evidenced by reduced amounts of myelin proteins and lipids and thinner myelin sheaths. In contrast, the optic nerve and spinal cord of heterozygotes are myelinated normally. Together, these results implicate type III NRG1 as a significant determinant of the extent of myelination in the brain and demonstrate important regional differences in the control of CNS myelination. They also indicate that oligodendrocyte myelination, but not differentiation, is promoted by axonal NRG1, underscoring important differences in the control of myelination in the CNS and peripheral nervous system (PNS).
authors: Department of Cell Biology, New York University School of Medicine, New York, New York, USA.
authors: Carla
authors: C
authors: Taveggia
authors: Pratik
authors: P
authors: Thaker
authors: Ashley
authors: A
authors: Petrylak
authors: Gregg L
authors: GL
authors: Caporaso
authors: Arrel
authors: A
authors: Toews
authors: Douglas L
authors: DL
authors: Falls
authors: Steven
authors: S
authors: Einheber
authors: James L
authors: JL
authors: Salzer
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000502:physiology; D001921:Brain / Q000166:cytology; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D005727:Ganglia, Spinal / Q000166:cytology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D050356:Lipid Metabolism; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009185:Myelin Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000502:physiology*; D020890:Neuregulin-1; D009474:Neurons; D009836:Oligodendroglia / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D010525:Peripheral Nerves / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection / Q000379:methods
chemical_list: D009185:Myelin Proteins; D009419:Nerve Tissue Proteins; D020890:Neuregulin-1; C490581:Nrg1 protein, mouse