Taveggia Carla, Thaker Pratik, Petrylak Ashley, Caporaso Gregg L, Toews Arrel, Falls Douglas L, Einheber Steven, Salzer James L
Department of Cell Biology, New York University School of Medicine, New York, New York, USA.
Glia. 2008 Feb;56(3):284-93. doi: 10.1002/glia.20612.
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).
在中枢神经系统（CNS）发育过程中，调节少突胶质细胞髓鞘形成的轴突信号尚未明确。在本研究中，我们检测了神经调节蛋白-1（NRG1）III型异构体对少突胶质细胞髓鞘形成的调节作用，NRG1是施万细胞分化和髓鞘形成所必需的一种神经元信号。与施万细胞不同，原代少突胶质细胞与III型NRG1缺陷的背根神经节（DRG）神经元共培养时能正常分化。然而，与野生型培养物相比，它们对III型NRG1缺陷的神经突髓鞘形成较差。III型NRG1不足以驱动少突胶质细胞髓鞘形成，因为即使通过慢病毒介导表达NRG1，交感神经元也不会被髓鞘化。III型NRG1单倍体不足的小鼠大脑髓鞘形成减少，髓磷脂蛋白和脂质含量降低以及髓鞘变薄证明了这一点。相比之下，杂合子的视神经和脊髓髓鞘形成正常。总之，这些结果表明III型NRG1是大脑髓鞘形成程度的一个重要决定因素，并证明了中枢神经系统髓鞘形成控制中重要的区域差异。它们还表明，轴突NRG1促进少突胶质细胞髓鞘形成，但不促进其分化，突出了中枢神经系统和周围神经系统（PNS）髓鞘形成控制中的重要差异。
