Analysis of myelinated axon formation in zebrafish.

Myelin is a lipid-rich sheath formed by the spiral wrapping of specialized glial cells around axon segments. Myelinating glia allow for rapid transmission of nerve impulses and metabolic support of axons, and the absence of or disruption to myelin results in debilitating motor, cognitive, and emotional deficits in humans. Because myelin is a jawed vertebrate innovation, zebrafish are one of the simplest vertebrate model systems to study the genetics and development of myelinating glia. The morphogenetic cellular movements and genetic program that drive myelination are conserved between zebrafish and mammals, and myelin develops rapidly in zebrafish larvae, within 3–5 days post-fertilization. Myelin ultrastructure can be visualized in the zebrafish from larval to adult stages via transmission electron microscopy, and the dynamic development of myelinating glial cells may be observed in vivo via transgenic reporter lines in zebrafish larvae. Zebrafish are amenable to genetic and pharmacological screens, and screens for myelinating glial phenotypes have revealed both genes and drugs that promote myelin development, many of which are conserved in mammalian glia. Recently, zebrafish have been employed as a model to understand the complex dynamics of myelinating glia during development and regeneration. In this chapter, we describe these key methodologies and recent insights into mechanisms that regulate myelination using the zebrafish model.

髓磷脂是一种富含脂质的鞘，由特化的神经胶质细胞围绕轴突节段螺旋状包裹形成。有髓神经胶质细胞使神经冲动能够快速传递，并为轴突提供代谢支持，而髓磷脂的缺失或受损会导致人类出现严重的运动、认知和情感缺陷。由于髓磷脂是有颌脊椎动物的一项创新，斑马鱼是研究有髓神经胶质细胞的遗传学和发育的最简单的脊椎动物模型系统之一。驱动髓鞘形成的形态发生细胞运动和遗传程序在斑马鱼和哺乳动物之间是保守的，并且髓磷脂在斑马鱼幼体受精后3 - 5天内迅速发育。通过透射电子显微镜可以观察到斑马鱼从幼体到成体阶段的髓磷脂超微结构，并且通过斑马鱼幼体的转基因报告基因系可以在体内观察到有髓神经胶质细胞的动态发育。斑马鱼适合进行遗传和药物筛选，对有髓神经胶质细胞表型的筛选已经揭示了促进髓磷脂发育的基因和药物，其中许多在哺乳动物的神经胶质细胞中是保守的。最近，斑马鱼已被用作一种模型来理解发育和再生过程中有髓神经胶质细胞的复杂动态。在本章中，我们描述了这些关键方法以及利用斑马鱼模型对调节髓鞘形成机制的最新见解。