Myelination of axons by oligodendrocytes and Schwann cells in the central and peripheral nervous system, respectively, is essential for normal neuronal functions, and its failure results in devastating demyelinating diseases. During development, both oligodendrocyte and Schwann cell precursors undergo a temporally well-defined series of molecular and structural changes, ultimately culminating in the cessation of proliferation and the elaboration of a highly complex myelin sheath. Recent studies have demonstrated a critical role of microRNAs (miRNAs) in the progression of oligodendrocyte and Schwann cell precursors to the myelinating state—depletion of miRNAs from either cell type results in an arrest in differentiation and lack of myelination. Furthermore, these studies have begun to elucidate the dynamic regulation of miRNA expression and the complexity of miRNA-mediated gene regulation during differentiation of myelinating cells. In this review, the authors highlight the recent understanding of functional links of miRNAs to regulatory networks for central and peripheral myelination, as well as perspectives on the role of miRNAs in demyelinating diseases.
AsirvathamAJGregorieCJHuZMagnerWJTomasiTB. 2008. MicroRNA targets in immune genes and the Dicer/Argonaute and ARE machinery components. Mol Immunol45(7):1995–2006.
2.
BartelDP. 2009. MicroRNAs: target recognition and regulatory functions. Cell136(2):215–33.
3.
BienvenuFJirawatnotaiSEliasJEMeyerCAMizerackaKMarsonA and others. 2010. Transcriptional role of cyclin D1 in development revealed by a genetic-proteomic screen. Nature463(7279):374-8.
4.
BremerJO’ConnorTTiberiCRehrauerHWeisJAguzziA. 2010. Ablation of Dicer from murine Schwann cells increases their proliferation while blocking myelination. PLoS One5(8):e12450.
5.
BuddeHSchmittSFitznerDOpitzLSalinas-RiesterGSimonsM. 2010. Control of oligodendroglial cell number by the miR-17-92 cluster. Development137(13):2127–32.
6.
CaoFLiXHiewSBradyHLiuYDouY. 2009. Dicer independent small RNAs associate with telomeric heterochromatin. RNA15(7):1274–81.
7.
ChongMMZhangGCheloufiSNeubertTAHannonGJLittmanDR. 2010. Canonical and alternate functions of the microRNA biogenesis machinery. Genes Dev24(17): 1951–60.
8.
DuCLiuCKangJZhaoGYeZHuangS and others. 2009. MicroRNA miR-326 regulates TH-17 differentiation and is associated with the pathogenesis of multiple sclerosis. Nat Immunol10(12):1252–9.
9.
DugasJCCuellarTLScholzeAAsonBIbrahimAEmeryB and others. 2010. Dicer1 and miR-219 are required for normal oligodendrocyte differentiation and myelination. Neuron65(5):597–611.
10.
EmeryB. 2010. Transcriptional and post-transcriptional control of CNS myelination. Curr Opin Neurobiol20(5):601–7.
11.
EmeryBAgalliuDCahoyJDWatkinsTADugasJCMulinyaweSB and others. 2009. Myelin gene regulatory factor is a critical transcriptional regulator required for CNS myelination. Cell138(1):172–85.
12.
FieldsRD. 2008. White matter matters. Sci Am298(3):42–9.
13.
GuoFMaJMcCauleyEBannermanPPleasureD. 2009. Early postnatal proteolipid promoter-expressing progenitors produce multilineage cells in vivo. J Neurosci29(22):7256–70.
HanJPedersenJSKwonSCBelairCDKimYKYeomKH and others. 2009. Posttranscriptional crossregulation between Drosha and DGCR8. Cell136(1):75–84.
16.
HebertSSDe StrooperB. 2007. Molecular biology. miRNAs in neurodegeneration. Science317(5842):1179–80.
17.
HoLFivecoatHWangJPasinettiGM. 2010. Alzheimer’s disease biomarker discovery in symptomatic and asymptomatic patients: experimental approaches and future clinical applications. Exp Gerontol45(1):15–22.
18.
IchimuraARuikeYTerasawaKShimizuKTsujimotoG. 2010. MicroRNA-34a inhibits cell proliferation by repressing mitogen-activated protein kinase kinase 1 during megakaryocytic differentiation of K562 cells. Mol Pharmacol77(6):1016–24.
19.
JessenKRMirskyR. 2005. The origin and development of glial cells in peripheral nerves. Nat Rev Neurosci6(9):671–82.
20.
JinekMDoudnaJA. 2009. A three-dimensional view of the molecular machinery of RNA interference. Nature457(7228): 405–12.
21.
JungMSchaeferASteinerIKempkensteffenCStephanCErbersdoblerA and others. 2010. Robust microRNA stability in degraded RNA preparations from human tissue and cell samples. Clin Chem56(6):998–1006.
22.
JunkerAKrumbholzMEiseleSMohanHAugsteinFBittnerR and others. 2009. MicroRNA profiling of multiple sclerosis lesions identifies modulators of the regulatory protein CD47. Brain132(Pt 12):3342–52.
23.
KaoSCWuHXieJChangCPRanishJAGraefIA and others. 2009. Calcineurin/NFAT signaling is required for neuregulin-regulated Schwann cell differentiation. Science323(5914):651–4.
24.
Kawase-KogaYOtaegiGSunT. 2009. Different timings of Dicer deletion affect neurogenesis and gliogenesis in the developing mouse central nervous system. Dev Dyn238(11):2800–12.
25.
KellerALeidingerPLangeJBorriesASchroersHSchefflerM and others. 2009. Multiple sclerosis: microRNA expression profiles accurately differentiate patients with relapsing-remitting disease from healthy controls. PLoS One4(10):e7440.
26.
KimJInoueKIshiiJVantiWBVoronovSVMurchisonE and others. 2007. A microRNA feedback circuit in midbrain dopamine neurons. Science317(5842):1220–4.
27.
KosikKS. 2006. The neuronal microRNA system. Nat Rev Neurosci7(12):911–20.
LalANavarroFMaherCAMaliszewskiLEYanNO’DayE and others. 2009. miR-24 Inhibits cell proliferation by targeting E2F2, MYC, and other cell-cycle genes via binding to “seedless” 3′UTR microRNA recognition elements. Mol Cell35(5):610–25.
30.
LauPVerrierJDNielsenJAJohnsonKRNotterpekLHudsonLD. 2008. Identification of dynamically regulated microRNA and mRNA networks in developing oligodendrocytes. J Neurosci28(45):11720–30.
31.
LawlerSChioccaEA. 2009. Emerging functions of microRNAs in glioblastoma. J Neurooncol92(3):297–306.
32.
LeNNagarajanRWangJYArakiTSchmidtREMilbrandtJ. 2005. Analysis of congenital hypomyelinating Egr2Lo/Lo nerves identifies Sox2 as an inhibitor of Schwann cell differentiation and myelination. Proc Natl Acad Sci U S A102(7):2596–601.
33.
LetzenBSLiuCThakorNVGearhartJDAllAHKerrCL. 2010. MicroRNA expression profiling of oligodendrocyte differentiation from human embryonic stem cells. PLoS One5(5):e10480.
34.
LiHHeYRichardsonWDCasacciaP. 2009. Two-tier transcriptional control of oligodendrocyte differentiation. Curr Opin Neurobiol19(5):479–85.
35.
LinSTFuYH. 2009. miR-23 regulation of lamin B1 is crucial for oligodendrocyte development and myelination. Dis Model Mech2(3–4):178–88.
36.
LiuNOlsonEN. 2010. MicroRNA regulatory networks in cardiovascular development. Dev Cell18(4):510–25.
37.
MaesOCChertkowHMWangESchipperHM. 2009. MicroRNA: implications for Alzheimer disease and other human CNS disorders. Curr Genomics10(3):154–68.
38.
MagerGMWardRMSrinivasanRJangSWWrabetzLSvarenJ. 2008. Active gene repression by the Egr2.NAB complex during peripheral nerve myelination. J Biol Chem283(26):18187–97.
39.
MirskyRWoodhooAParkinsonDBArthur-FarrajPBhaskaranAJessenKR. 2008. Novel signals controlling embryonic Schwann cell development, myelination and dedifferentiation. J Peripher Nerv Syst13(2):122–35.
40.
NaveKA. 2010. Oligodendrocytes and the “micro brake” of progenitor cell proliferation. Neuron65(5):577–9.
41.
NaveKATrappBD. 2008. Axon-glial signaling and the glial support of axon function. Annu Rev Neurosci31:535–61.
42.
NovakovaJSlabyOVyzulaRMichalekJ. 2009. MicroRNA involvement in glioblastoma pathogenesis. Biochem Biophys Res Commun386(1):1–5.
43.
OldenborgPAZheleznyakAFangYFLagenaurCFGreshamHDLindbergFP. 2000. Role of CD47 as a marker of self on red blood cells. Science288(5473):2051–4.
44.
OtaeguiDBaranziniSEArmananzasRCalvoBMunoz-CullaMKhankhanianP and others. 2009. Differential micro RNA expression in PBMC from multiple sclerosis patients. PLoS One4(7):e6309.
45.
PangRTLeungCOYeTMLiuWChiuPCLamKK and others. 2010. MicroRNA-34a suppresses invasion through downregulation of Notch1 and Jagged1 in cervical carcinoma and choriocarcinoma cells. Carcinogenesis31(6): 1037–44.
46.
ParkinsonDBBhaskaranAArthur-FarrajPNoonLAWoodhooALloydAC and others. 2008. c-Jun is a negative regulator of myelination. J Cell Biol181(4):625–37.
47.
PereiraJABaumannRNorrmenCSomandinCMieheMJacobC and others. 2010. Dicer in Schwann cells is required for myelination and axonal integrity. J Neurosci30(19): 6763–75.
48.
PeruRLMandryckyNNait-OumesmarBLuQR. 2008. Paving the axonal highway: from stem cells to myelin repair. Stem Cell Rev4(4):304–18.
49.
PotznerMRTsarovinaKBinderEPenzo-MendezALefebvreVRohrerH and others. 2010. Sequential requirement of Sox4 and Sox11 during development of the sympathetic nervous system. Development137(5):775–84.
SantoshPSAroraNSarmaPPal-BhadraMBhadraU. 2009. Interaction map and selection of microRNA targets in Parkinson’s disease-related genes. J Biomed Biotechnol2009:363145.
52.
SchererSSWrabetzL. 2008. Molecular mechanisms of inherited demyelinating neuropathies. Glia56(14):1578–89.
53.
SchwartzJCYoungerSTNguyenNBHardyDBMoniaBPCoreyDR and others. 2008. Antisense transcripts are targets for activating small RNAs. Nat Struct Mol Biol15(8):842–8.
54.
ShinDShinJYMcManusMTPtacekLJFuYH. 2009. Dicer ablation in oligodendrocytes provokes neuronal impairment in mice. Ann Neurol66(6):843–57.
55.
TayYZhangJThomsonAMLimBRigoutsosI. 2008. MicroRNAs to Nanog, Oct4 and Sox2 coding regions modulate embryonic stem cell differentiation. Nature455(7216): 1124–8.
56.
TopilkoPSchneider-MaunourySLeviGBaron-Van EvercoorenAChennoufiABSeitanidouT and others. 1994. Krox-20 controls myelination in the peripheral nervous system. Nature371(6500):796–9.
57.
TrappBDNaveKA. 2008. Multiple sclerosis: an immune or neurodegenerative disorder?Annu Rev Neurosci31:247–69.
58.
VasudevanSTongYSteitzJA. 2007. Switching from repression to activation: microRNAs can up-regulate translation. Science318(5858):1931–4.
59.
VenturaAYoungAGWinslowMMLintaultLMeissnerAErkelandSJ and others. 2008. Targeted deletion reveals essential and overlapping functions of the miR-17 through 92 family of miRNA clusters. Cell132(5):875–86.
60.
VerrierJDLauPHudsonLMurashovAKRenneRNotterpekL. 2009. Peripheral myelin protein 22 is regulated post-transcriptionally by miRNA-29a. Glia57(12): 1265–79.
61.
VerrierJDSemple-RowlandSMadorskyIPapinJENotterpekL. 2010. Reduction of Dicer impairs Schwann cell differentiation and myelination. J Neurosci Res88(12): 2558–68.
62.
VoNKCambronneXAGoodmanRH. 2010. MicroRNA pathways in neural development and plasticity. Curr Opin Neurobiol20(4):457–65.
63.
WegnerM. 2008. A matter of identity: transcriptional control in oligodendrocytes. J Mol Neurosci35(1):3–12.
64.
WoodhooAAlonsoMBDroggitiATurmaineMD’AntonioMParkinsonDB and others. 2009. Notch controls embryonic Schwann cell differentiation, postnatal myelination and adult plasticity. Nat Neurosci12(7):839-47.
65.
XuNPapagiannakopoulosTPanGThomsonJAKosikKS. 2009. MicroRNA-145 regulates OCT4, SOX2, and KLF4 and represses pluripotency in human embryonic stem cells. Cell137(4):647–58.
66.
YuYCasacciaPLuQR. 2010. Shaping the oligodendrocyte identity by epigenetic control. Epigenetics5(2):124–8.
ZhaoXHeXHanXYuYYeFChenY and others. 2010. MicroRNA-mediated control of oligodendrocyte differentiation. Neuron65(5):612–26.
69.
ZhengKLiHZhuYZhuQQiuM. 2010. MicroRNAs are essential for the developmental switch from neurogenesis to gliogenesis in the developing spinal cord. J Neurosci30(24):8245–50.
