Seeing Is Believing: Insights into Myelination and Remyelination in Zebrafish

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.