PUBLICATION

MicroRNA-Mediated Control of Oligodendrocyte Differentiation

Authors
Zhao, X., He, X., Han, X., Yu, Y., Ye, F., Chen, Y., Hoang, T., Xu, X., Mi, Q.S., Xin, M., Wang, F., Appel, B., and Lu, Q.R.
ID
ZDB-PUB-100317-22
Date
2010
Source
Neuron   65(5): 612-626 (Journal)
Registered Authors
Appel, Bruce
Keywords
MOLNEURO
MeSH Terms
  • Oligodendroglia/drug effects
  • Oligodendroglia/physiology*
  • Cerebral Cortex/cytology
  • Models, Biological
  • Embryo, Nonmammalian
  • Cell Differentiation/drug effects
  • Cell Differentiation/genetics*
  • RNA, Small Interfering/pharmacology
  • Embryo, Mammalian
  • SOXD Transcription Factors/genetics
  • SOXD Transcription Factors/metabolism
  • Rats
  • Ribonuclease III
  • Mice, Knockout
  • MicroRNAs/metabolism*
  • Basic Helix-Loop-Helix Transcription Factors/genetics
  • Basic Helix-Loop-Helix Transcription Factors/metabolism
  • Endoribonucleases/deficiency
  • Myelin Sheath/metabolism
  • Hippocampus/cytology
  • Spinal Cord/embryology
  • Spinal Cord/growth & development
  • Spinal Cord/metabolism
  • Electroporation/methods
  • Animals
  • Chick Embryo
  • Stem Cells/drug effects
  • Stem Cells/physiology*
  • DEAD-box RNA Helicases/deficiency
  • Gene Expression Regulation, Developmental/genetics
  • Zebrafish
  • Neurons/drug effects
  • Neurons/physiology
  • Cells, Cultured
  • Mice
PubMed
20223198 Full text @ Neuron
Abstract
MicroRNAs (miRNAs) regulate various biological processes, but evidence for miRNAs that control the differentiation program of specific neural cell types has been elusive. To determine the role of miRNAs in the formation of myelinating oligodendrocytes, we selectively deleted a miRNA-processing enzyme, Dicer1, in oligodendrocyte lineage cells. Mice lacking Dicer1 display severe myelinating deficits despite an expansion of the oligodendrocyte progenitor pool. To search for miRNAs responsible for the induction of oligodendrocyte maturation, we identified miR-219 and miR-338 as oligodendrocyte-specific miRNAs in spinal cord. Overexpression of these miRNAs is sufficient to promote oligodendrocyte differentiation. Additionally, blockage of these miRNA activities in oligodendrocyte precursor culture and knockdown of miR-219 in zebrafish inhibit oligodendrocyte maturation. miR-219 and miR-338 function in part by directly repressing negative regulators of oligodendrocyte differentiation, including transcription factors Sox6 and Hes5. These findings illustrate that miRNAs are important regulators of oligodendrocyte differentiation, providing new targets for myelin repair.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping