Dynamic Process And Mechanisms Of Myelin Development

Axon-wrapping myelin sheath is essential for proper functioning of the nervoussystem. Myelin is formed from membranous sheets that are elaborated byoligodendrocytes (OLs) in the central nervous system (CNS). Although much isknown about the development and migration of OL and its progenitor cell in vitro andin vivo, how CNS myelin is dynamically formed through OL processes is still unclear.To examine the process of CNS myelination in vivo, we performed long-termtime-lapse confocal imaging of the same OLs in the spinal cord of intact zebrafishlarvae during2–7days post-fertilization (dpf) with intervals of2–12hr. IndividualOLs were mosaically labeled by membrane-tethered red fuorescent protein (mRFP)under the control of zebrafish Sox10regulatory DNA. We find that, besides extensionof some early-stage axon-wrapping myelin segments,28%segments undergo pruningin an axon diameter-correlated manner during early development. Down-regulatingneuregulin-ErbB signaling impairs the pruning but not extension. On the other hand,we also find that in the ventral spinal cord, myelin sheath segments extenddirectionally to the anterior side of the zebrafish larva. Further experimentsdemonstrate that Wnt signaling activation shows anterior to posterior grandients anddown-regulating Wnt signaling impairs the myelin segments directional extension.Furthermore, this growth pattern may facilitate the Homogenization of myelinsegments length and the rapid saltatory conduction of neural activity. Thus our resultsindicate myelin segments pruning and directional extension as novel growth patternduring development of oligodendrocyte in vivo.