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.
Zhao
Xianghui
X
Department of Developmental Biology and Kent Waldrep Foundation Center for Basic Neuroscience Research on Nerve Growth and Regeneration, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
He
Xuelian
X
Han
Xiaolei
X
Yu
Yang
Y
Ye
Feng
F
Chen
Ying
Y
Hoang
ThaoNguyen
T
Xu
Xiaomei
X
Mi
Qing-Sheng
QS
Xin
Mei
M
Wang
Fan
F
Appel
Bruce
B
Lu
Q Richard
QR
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D002642:Chick Embryo; D053487:DEAD-box RNA Helicases / Q000172:deficiency; D018274:Electroporation / Q000379:methods; D004622:Embryo, Mammalian; D004625:Embryo, Nonmammalian; D004722:Endoribonucleases / Q000172:deficiency; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006624:Hippocampus / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000378:metabolism*; D008954:Models, Biological; D009186:Myelin Sheath / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009836:Oligodendroglia / Q000187:drug effects / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D043244:Ribonuclease III; D055755:SOXD Transcription Factors / Q000235:genetics / Q000378:metabolism; D013116:Spinal Cord / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology*; D015027:Zebrafish
D051792:Basic Helix-Loop-Helix Proteins; D053487:DEAD-box RNA Helicases; D004722:Endoribonucleases; D035683:MicroRNAs; D034741:RNA, Small Interfering; D043244:Ribonuclease III; D055755:SOXD Transcription Factors; C509781:Dicer1 protein, mouse