Dissecting mechanisms of myelinated axon formation using zebrafish

The myelin sheath is an essential component of the vertebrate nervous system, and its disruption causes numerous diseases, including multiple sclerosis (MS), and neurodegeneration. Although we understand a great deal about the early development of the glial cells that make myelin (Schwann cells in the peripheral nervous system and oligodendrocytes in the central nervous system), we know much less about the cellular and molecular mechanisms that regulate the later stages of differentiation that orchestrate myelin formation. Over the past decade, the zebrafish has been employed as a model with which to dissect the development of myelinated axons. Forward genetic screens have revealed new genes essential for myelination, as well as new roles for genes previously implicated in myelinated axon formation in other systems. High-resolution in vivo imaging in zebrafish has also begun to illuminate novel cell behaviors during myelinating glial cell development. Here we review the contribution of zebrafish research to our understanding of myelinated axon formation to date. We also describe and discuss many of the methodologies used in these studies and preview future endeavors that will ensure that the zebrafish remains at the cutting edge of this important area of research.