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
-
- Rats
- Embryo, Nonmammalian
- Gene Expression Regulation, Developmental/genetics
- Animals
- Electroporation/methods
- SOXD Transcription Factors/genetics
- SOXD Transcription Factors/metabolism
- MicroRNAs/metabolism*
- Cells, Cultured
- Mice, Knockout
- Embryo, Mammalian
- Basic Helix-Loop-Helix Transcription Factors/genetics
- Basic Helix-Loop-Helix Transcription Factors/metabolism
- Ribonuclease III
- Cell Differentiation/drug effects
- Cell Differentiation/genetics*
- Cerebral Cortex/cytology
- Stem Cells/drug effects
- Stem Cells/physiology*
- Hippocampus/cytology
- DEAD-box RNA Helicases/deficiency
- Models, Biological
- Myelin Sheath/metabolism
- RNA, Small Interfering/pharmacology
- Mice
- Zebrafish
- Spinal Cord/embryology
- Spinal Cord/growth & development
- Spinal Cord/metabolism
- Neurons/drug effects
- Neurons/physiology
- Oligodendroglia/drug effects
- Oligodendroglia/physiology*
- Endoribonucleases/deficiency
- Chick Embryo
- PubMed
- 20223198 Full text @ Neuron
Citation
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. (2010) MicroRNA-Mediated Control of Oligodendrocyte Differentiation. Neuron. 65(5):612-626.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping