Sox10 is necessary for oligodendrocyte survival following axon wrapping.
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.
Department of Pediatrics, University of Colorado Denver Anshutz Medical Campus, Aurora, Colorado 80045, USA.
Norio
N
Takada
Sarah
S
Kucenas
Bruce
B
Appel
D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000378:metabolism*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D001973:Bromodeoxyuridine / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D004625:Embryo, Nonmammalian; D053595:Embryonic Stem Cells / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000235:genetics; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins / Q000378:metabolism; D007814:Larva; D009419:Nerve Tissue Proteins / Q000235:genetics; D000076104:Oligodendrocyte Transcription Factor 2; D009836:Oligodendroglia / Q000502:physiology*; D055757:SOXE Transcription Factors / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
D051792:Basic Helix-Loop-Helix Proteins; D001973:Bromodeoxyuridine; D053148:Caspase 3; D049452:Green Fluorescent Proteins; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D055757:SOXE Transcription Factors; D014157:Transcription Factors; D029961:Zebrafish Proteins; C485184:enhanced green fluorescent protein; C465361:olig2 protein, zebrafish; C442229:sox10 protein, zebrafish