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MicroRNA-mediated control of oligodendrocyte differentiation.

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.

Pubmed ID: 20223198


  • Zhao X
  • He X
  • Han X
  • Yu Y
  • Ye F
  • Chen Y
  • Hoang T
  • Xu X
  • Mi QS
  • Xin M
  • Wang F
  • Appel B
  • Lu QR



Publication Data

March 11, 2010

Associated Grants

  • Agency: NINDS NIH HHS, Id: NS050389
  • Agency: NINDS NIH HHS, Id: R01 NS046668
  • Agency: NINDS NIH HHS, Id: R01 NS050389
  • Agency: NINDS NIH HHS, Id: R01 NS050389-05

Mesh Terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Differentiation
  • Cells, Cultured
  • Cerebral Cortex
  • Chick Embryo
  • DEAD-box RNA Helicases
  • Electroporation
  • Embryo, Mammalian
  • Embryo, Nonmammalian
  • Endoribonucleases
  • Gene Expression Regulation, Developmental
  • Hippocampus
  • Mice
  • Mice, Knockout
  • MicroRNAs
  • Models, Biological
  • Myelin Sheath
  • Neurons
  • Oligodendroglia
  • RNA, Small Interfering
  • Rats
  • Ribonuclease III
  • SOXD Transcription Factors
  • Spinal Cord
  • Stem Cells
  • Zebrafish