Macro Roles for Micrornas in the Life and Death of Neurons

ThediscoveryofmicroRNAshasrevealedanunexpectedandspectacularadditional levelof?netuningofthegenomeandhowgenesareusedagainandagainin differentcombinationstogeneratethecomplexitythatunderliesforinstancethe brain. SincetheinitialstudiesperformedinC. elegans, wegavegoneafarwayto begintounderstandhowmicroRNApathwayscanhaveanimpactonhealthand diseaseinhuman. AlthoughmicroRNAsareabundantlyexpressedinthebrain, relativelylittleisknownaboutthemultiplefunctionsoftheseRNAmoleculesinthe nervous system. Nevertheless, we knowalready that microRNA pathways play majorrolesintheproliferation, differentiation, functionandmaintenanceofneu- nalcells. SeveralintriguingstudieshavelinkedmicroRNAsasmajorregulatorsof theneuronalphenotype, andhaveimplicatedspeci?cmicroRNAsintheregulation ofsynapseformationandplasticity. DysfunctionofmicroRNApathwaysisalso slowlyemergingasapotentialimportantcontributortothepathogenesisofmajor neurodegenerativedisorderssuchasAlzheimer'sdiseaseandParkinson'sdisease. Thesenovelinsightsappeartobeparticularpromisingfortheunderstandingofthe veryfrequentandbadlyunderstoodsporadicformsofthesediseasesascomparedto thegeneticforms. Thus, thebetterunderstandingoftheimplicationsofthisnovel ?eldofmolecularbiologyiscrucialforthebroadareaofneurosciences, fromthe fundamentalaspectstotheclinic, andfromnoveldiagnostictopotentiallythe- peuticapplicationsforsevereneurologicalandmaybepsychiatricdiseases. The presentvolumegatherscontributionstotheColloqueMe´decineetRechercheonthe implicationsofmicroRNAsinneuroscienceorganizedbytheFondationIpsen, in Paris, onApril20,2009. Ithadasobjectivetobringtogetherneuroscientistsfrom differentareasofresearchtodiscusstheircurrentinsightsintothewonderfulworld ofmicroRNAs, andtohearanddiscusstheirresearchandviewsaboutmicroRNA biologyinneuronalprocessesandinbraindisorders. BartdeStrooper YvesChristen v Acknowledgments The editors wish to thank Jacqueline Mervaillie and Sonia Le Cornec for the organizationofthemeetingandMaryLynnGagefortheeditingofthebook. vii Contents Pro?lingthemicroRNAs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 KennethS. Kosik, ThalesPapagiannakopoulos, NaXu, KawtherAbu-Elneel, TsunglinLiu, andMinJeongKye TheWideVarietyofmiRNAExpressionPro?les intheDevelopingandMatureCNS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 MarikaKapsimali InteractionsbetweenmicroRNAsandTranscription FactorsintheDevelopmentandFunction oftheNervousSystem . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 DavidJ. Simon AmicroRNAFeedbackCircuitinMidbrainDopamineNeurons . . . . . . . . . 27 AsaAbeliovich Fine-tuningmRNATranslationatSynapseswithmicroRNAs . . . . . . . . . . . . 35 GerhardM. Schratt NeuronalP-bodiesandTransportofmicroRNA-Repressed mRNAs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 FlorenceRage CrosstalkbetweenmicroRNAandEpigeneticRegulation inStemCells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57 KeithSzulwach, ShuangChang, andPengJin microRNAsinCNSDevelopmentandNeurodegeneration: InsightsfromDrosophilaGenetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69 StephenM. Cohen ix x Contents DrosophilaasaModelforNeurodegenerativeDisease: RolesofRNAPathwaysinPathogenesis . . . . . . .