Schebesta Michael, Serluca Fabrizio C
Developmental and Molecular Pathways, Novartis Institutes for Biomedical Research, Cambridge, Massachusetts 02139, USA.
Dev Dyn. 2009 Apr;238(4):887-98. doi: 10.1002/dvdy.21909.
Myelin, the isolating sheath around large diameter axons, is formed in the central nervous system (CNS) by oligodendrocytes. We isolated the zebrafish ortholog of olig1, a bHLH transcription factor, and describe the origin and development of oligodendrocytes in the zebrafish brain. Olig1:mem-eGFP transgenic animals demonstrate the highly dynamic nature of oligodendrocyte membrane processes, providing a tool for studying in vivo oligodendrocyte development. Formation of oligodendrocytes and initiation of olig1 expression are under the control of long-range hedgehog and notch signaling while maintenance of olig1 expression only depends on hedgehog. Over-expression of olig1 did not affect myelin formation in the brain and combined over-expression of olig1 and olig2 could not rescue loss of hedgehog signaling, indicating that critical factors other than olig1 and olig2 are necessary. Lastly, knockdown of Olig1 in an Olig2-sensitized background did result in defects in CNS myelination, indicating a functional overlap between Olig1 and Olig2 proteins.
髓磷脂是围绕大直径轴突的绝缘鞘，在中枢神经系统（CNS）中由少突胶质细胞形成。我们分离出了少突胶质细胞转录因子1（olig1）的斑马鱼直系同源物，并描述了斑马鱼大脑中少突胶质细胞的起源和发育。Olig1:mem-eGFP转基因动物展示了少突胶质细胞膜突起的高度动态特性，为研究体内少突胶质细胞发育提供了一个工具。少突胶质细胞的形成和olig1表达的起始受远程刺猬信号通路和Notch信号通路的控制，而olig1表达的维持仅依赖于刺猬信号通路。olig1的过表达不影响大脑中的髓磷脂形成，olig1和olig2的联合过表达不能挽救刺猬信号通路缺失的情况，这表明除了olig1和olig2之外，其他关键因子也是必需的。最后，在Olig2敏感背景下敲低Olig1确实导致了中枢神经系统髓鞘形成缺陷，这表明Olig1和Olig2蛋白之间存在功能重叠。
