Liu Peng, Chen Qiang, He Cheng
Institute of Neuroscience and Key Laboratory of Molecular Neurobiology of Ministry of Education, Naval Medical University, Shanghai, China.
Adv Neurobiol. 2025;43:81-95. doi: 10.1007/978-3-031-87919-7_4.
Myelin is the lipid-rich insulating layer that wraps axons, providing trophic support and ensuring rapid propagation of the electrical impulses that underlie nervous system function. In the CNS, myelin is produced by mature oligodendrocytes (OLs) that arise from oligodendrocyte precursor cells (OPCs). Myelination is regulated by a variety of molecules, including growth factors, hormones, and extracellular molecules, which activate signaling cascades that drive cellular maturation. Key signaling molecules and downstream pathways that control myelination have been identified in cell culture and rodent models. Although much is known about the development of OL and its progenitor cell in vitro and in vivo, how CNS myelin is dynamically formed through OL processes is still unclear. Zebrafish share significant genetic and physiological similarities with mammals, including humans, making them a relevant model for studying complex biological processes like myelination. Due to its transparent larval development, zebrafish facilitates live imaging studies, enabling dynamic visualizations of cellular and molecular processes in real-time studies. In this chapter, we reviewed the latest insights into OL development and myelin formation, with a particular emphasis on the mechanisms regulating dynamic myelination in zebrafish. We highlight the dynamic extension and retraction of myelin sheath segments and the role of neuronal activity in regulating the developmental myelination in zebrafish. In addition, we also discussed the mechanisms of Ranvier node positioning and axon targeting of myelin sheaths in the spinal cord of zebrafish larvae. Finally, we reviewed the recent progress of zebrafish as a demyelinating disease model for drug discovery of pharmacological compounds favoring myelin regeneration.
髓磷脂是富含脂质的绝缘层，包裹着轴突，提供营养支持并确保构成神经系统功能基础的电冲动快速传播。在中枢神经系统中，髓磷脂由源自少突胶质前体细胞（OPC）的成熟少突胶质细胞（OL）产生。髓鞘形成受多种分子调节，包括生长因子、激素和细胞外分子，这些分子激活驱动细胞成熟的信号级联反应。在细胞培养和啮齿动物模型中已鉴定出控制髓鞘形成的关键信号分子和下游途径。尽管在体外和体内对OL及其祖细胞的发育了解很多，但中枢神经系统髓磷脂如何通过OL过程动态形成仍不清楚。斑马鱼与包括人类在内的哺乳动物具有显著的遗传和生理相似性，使其成为研究髓鞘形成等复杂生物学过程的相关模型。由于其幼虫发育透明，斑马鱼便于进行活体成像研究，能够在实时研究中对细胞和分子过程进行动态可视化。在本章中，我们回顾了OL发育和髓鞘形成的最新见解，特别强调了调节斑马鱼动态髓鞘形成的机制。我们强调了髓鞘鞘段的动态延伸和收缩以及神经元活动在调节斑马鱼发育性髓鞘形成中的作用。此外，我们还讨论了斑马鱼幼虫脊髓中朗飞结定位和髓鞘鞘轴突靶向的机制。最后，我们回顾了斑马鱼作为脱髓鞘疾病模型在发现促进髓鞘再生的药理化合物药物方面的最新进展。
