MicroRNA-Mediated Control of Oligodendrocyte Differentiation

Xianghui Zhao, Xuelian He, Xiaolei Han, Yang Yu, Feng Ye, Ying Chen, ThaoNguyen Hoang, Xiaomei Xu, Qing Sheng Mi, Mei Xin, Fan Wang, Bruce Appel, Q. Richard Lu

Research output: Contribution to journalArticle

331 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)612-626
Number of pages15
JournalNeuron
Volume65
Issue number5
DOIs
StatePublished - Mar 11 2010

Keywords

  • MOLNEURO

ASJC Scopus subject areas

  • Neuroscience(all)

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  • Cite this

    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., & Lu, Q. R. (2010). MicroRNA-Mediated Control of Oligodendrocyte Differentiation. Neuron, 65(5), 612-626. https://doi.org/10.1016/j.neuron.2010.02.018