Sox10 is necessary for oligodendrocyte survival following axon wrapping

Takada, N., Kucenas, S., and Appel, B.
Glia   58(8): 996-1006 (Journal)
Registered Authors
Appel, Bruce, Kucenas, Sarah, Takada, Norio
Glia, myelin, CNS development, zebrafish, glia-neuron interaction, glia differentiation, Nkx2.2, Olig2
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Axons/metabolism*
  • Basic Helix-Loop-Helix Transcription Factors/genetics
  • Bromodeoxyuridine/metabolism
  • Caspase 3/metabolism
  • Cell Differentiation/genetics
  • Cell Movement/genetics
  • Cell Survival/genetics
  • Embryo, Nonmammalian
  • Embryonic Stem Cells/physiology
  • Gene Expression Regulation, Developmental/genetics*
  • Green Fluorescent Proteins/genetics
  • Homeodomain Proteins/metabolism
  • Larva
  • Nerve Tissue Proteins/genetics
  • Oligodendroglia/physiology*
  • SOXE Transcription Factors/genetics
  • SOXE Transcription Factors/metabolism*
  • Time Factors
  • Transcription Factors/metabolism
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
20229602 Full text @ Glia
Cells of the oligodendrocyte lineage, which form the myelinating glia of the vertebrate central nervous system, undergo a stepwise developmental progression entailing specification from neuroepithelial precursors, proliferation, migration to expand and distribute the population, and differentiation to ensheath axons with myelin. Understanding the genetic mechanisms that regulate each of these steps during development is important, because this might lead to therapies to promote remyelination following neural injury or disease. Genetic studies in mice indicated that the Sox10 transcription factor is required during the differentiation stage to promote myelin gene expression. However, whether Sox10 also promotes other features of oligodendroctye differentiation remained unknown. In this study, we used time-lapse imaging to investigate the behavior and fates of oligodendrocyte lineage cells in zebrafish embryos and larvae that lacked Sox10 function. This revealed that the myelinating subset of oligodendrocyte progenitor cells (OPCs) migrates, divides, and wraps axons normally, but then dies. Nonmyelinating oligodendrocyte progenitors divided more frequently, maintaining a normal population size. New oligodendrocytes produced by these progenitors wrapped axons and survived, but did not express myelin genes at high levels. We conclude that, in addition to promoting myelin gene expression, Sox10 function is necessary for the survival of myelinating oligodedrocytes subsequent to axon wrapping but is not required for the survival of nonmyelinating OPCs.
Genes / Markers
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes