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 ...4 5
FlorenceRage CrosstalkbetweenmicroRNAandEpigeneticRegulation
inStemCells ...57 KeithSzulwach,ShuangChang,andPengJin
microRNAsinCNSDevelopmentandNeurodegeneration:
InsightsfromDrosophilaGenetics ...69 StephenM. Cohen ix x Contents
DrosophilaasaModelforNeurodegenerativeDisease:
RolesofRNAPathwaysinPathogenesis ...79 NancyM. Bonini
microRNAsinSporadicAlzheimer'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 ...79 NancyM. Bonini
microRNAsinSporadicAlzheimer'sDiseaseandRelated Dementias ...91
Se'bastienS. He'bert,WimMandemakers,AikateriniS. Papadopoulou,
andBartDeStrooper microRNADysregulationinPsychiatricDisorders ...99
BinXu,JosephA. Gogos,andMariaKarayiorgou Index ...1 19 Contributors
Abeliovich Asa Columbia University Medical Center, 630 West 168th
Street, Room15-405,NewYork,NY10032,USA,aa900@columbia. edu
Abu-ElneelKawther
NeuroscienceResearchInstitute,DepartmentofMolecular
CellularandDevelopmentalBiology,UniversityofCaliforniaSantaBarbara,USA
BoniniNancyM. UniversityofPennsylvania,306LeidyLaboratories,Depa-
mentofBiology,Philadelphia,PA19104,USA,nbonini@sas. upenn. edu
Chang Shuang Department of Human Genetics, Emory University School
of Medicine,Atlanta,GA30322,USA CohenStephenM.
TemasekLifeSciencesLaboratoryLimited,1ResearchLink National
University of Singapore, 117604 Singapore, SINGAPORE, steve@ tll.
org. sg DeStrooperBart Centerforhumangenetics,K. U.
LeuvenandDepartmentof
molecularanddevelopmentalgenetics,VIBLeuven,BELGIUM GogosJosephA.
DepartmentofPhysiology&CellularBiophysicsandDepa-
mentofNeuroscience,ColumbiaUniversity,NewYork,USA He'bert
Se'bastien S. Centre de Recherche du CHUQ (CHUL), Axe Neur-
ciences,Universite'Laval,De'partementdeBiologieme'dicale,2705Boul.
Laurier, LocalRC-9800,Que'bec,Qc,Canada,sebastien. hebert@crchul.
ulaval. ca JinPeng
DepartmentofHumanGeneticsandGraduatePrograminGeneticsand
MolecularBiology,EmoryUniversitySchoolofMedicine,Atlanta,GA30322,
USA,pjin@genetics. emory. edu ' ' ' ' KapsimaliMarika
INSERMU784,GenetiqueMoleculaireduDeveloppement, ' Ecole Normale
Superieure, 46 rue d'Ulm, 75230 PARIS Cedex 05 FRANCE,
kapsimal@biologie. ens. fr xi xii Contributors Karayiorgou Maria
Columbia University, Department of Psychiatry, 1051
RiversideDrive,Unit#28,NewYorkNY10032,USA,mk2758@columbia. edu
Kosik Kenneth S. Neuroscience Research Institute, Department of
Molecular Cellular and Developmental Biology, University of
California Santa Barbara,
BiologyII,Room6139A,SantaBarbara,CA93106,USA,kosik@lifesci. ucsb.
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