Abstract

BackgroundIn the developing central nervous system, pre-myelinating oligodendrocytes sample candidate nerve axons by extending and retracting process extensions. Some contacts stabilize, leading to the initiation of axon wrapping, nascent myelin sheath formation, concentric wrapping and sheath elongation, and sheath stabilization or pruning by oligodendrocytes. Although axonal signals influence the overall process of myelination, the precise oligodendrocyte behaviors that require signaling from axons are not completely understood. In this study, we investigated whether oligodendrocyte behaviors during the early events of myelination are mediated by an oligodendrocyte-intrinsic myelination program or are over-ridden by axonal factors.MethodsTo address this, we utilized in vivo time-lapse imaging in embryonic and larval zebrafish spinal cord during the initial hours and days of axon wrapping and myelination. Transgenic reporter lines marked individual axon subtypes or oligodendrocyte membranes.ResultsIn the larval zebrafish spinal cord, individual axon subtypes supported distinct nascent sheath growth rates and stabilization frequencies. Oligodendrocytes ensheathed individual axon subtypes at different rates during a two-day period after initial axon wrapping. When descending reticulospinal axons were ablated, local spinal axons supported a constant ensheathment rate despite the increased ratio of oligodendrocytes to target axons.ConclusionWe conclude that properties of individual axon subtypes instruct oligodendrocyte behaviors during initial stages of myelination by differentially controlling nascent sheath growth and stabilization.

Highlights

  • In the developing central nervous system, pre-myelinating oligodendrocytes sample candidate nerve axons by extending and retracting process extensions

  • Single oligodendrocytes can extend processes into and form myelin sheaths within both dorsal and ventral white matter tracts, which are composed of unique axon populations

  • To determine how oligodendrocyte behaviors are influenced by different axon subtypes, we first identified myelin-competent target axons within the larval zebrafish spinal cord

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Summary

Introduction

In the developing central nervous system, pre-myelinating oligodendrocytes sample candidate nerve axons by extending and retracting process extensions. Oligodendrocytes are specialized central nervous system (CNS) ensheathing cells that extend multiple membrane processes to sample candidate axons, initiate and perform spiral axon wrapping, extend along axons to form a mature myelin sheath (reviewed by [1, 2]). Oligodendrocytes can retract and prune myelin sheaths [3,4,5], as well as modify the thickness of individual sheaths in response to external stimuli [6] These complex steps take place over the course of days or weeks, and are responsible for mature myelin sheaths being positioned at the right location, time, and parameters [7,8,9].

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