Functional Dicer Is Necessary for Appropriate Specification of Radial Glia during Early Development of Mouse Telencephalon 英文参考文献.docVIP

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Functional Dicer Is Necessary for Appropriate Specification of Radial Glia during Early Development of Mouse Telencephalon 英文参考文献.doc

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Functional Dicer Is Necessary for Appropriate Specification of Radial Glia during Early Development of Mouse Telencephalon 英文参考文献

FunctionalDicerIsNecessaryforAppropriate SpecificationofRadialGliaduringEarlyDevelopmentof MouseTelencephalon TomaszJanNowakowski*,KarolinaSandraMysiak,ThomasPratt,DavidJonathanPrice DevelopmentalBiologyLaboratory,CentreforIntegrativePhysiology,UniversityofEdinburgh,Edinburgh,UnitedKingdom Abstract Earlytelencephalicdevelopmentinvolvestransformationofneuroepithelialstemcellsintoradialglia,whicharethemselves neuronal progenitors, around the time when the tissue begins to generate postmitotic neurons. To achieve this transformation,radialprecursorsexpressaspecificcombinationofproteins.WeinvestigatethehypothesisthatmicroRNAs regulate the ability of the early telencephalic progenitors to establish radial glia. We ablate functional Dicer, which is required for the generation of mature micro RNAs, by conditionally mutating the Dicer1 gene in the early embryonic telencephalonandanalysethemolecularspecificationofradialgliaaswellastheirprogeny,namelypostmitoticneurons andbasalprogenitors.ConditionalmutationofDicer1fromthetelencephalonataroundembryonicday8doesnotprevent morphologicaldevelopmentofradialglia,buttheirexpressionofNestin,Sox9,andErbB2isabnormallylow.Thepopulation ofbasalprogenitors,whicharegeneratedbytheradialglia,isdisorganisedandexpandedinDicer1-/-dorsaltelencephalon. While the proportion of cells expressing markers of postmitotic neurons is unchanged, their laminar organisation in the telencephalicwallisdisruptedsuggestingadefectinradialglialguidedmigration.Wefoundthatthelaminardisruption couldnotbeaccountedforbyareductionofthepopulationofCajalRetziusneurons.Together,ourdatasuggestnovel rolesformicroRNAsduringearlydevelopmentofprogenitorcellsintheembryonictelencephalon. Citation:NowakowskiTJ,MysiakKS,PrattT,PriceDJ(2011)FunctionalDicerIsNecessaryforAppropriateSpecificationofRadialGliaduringEarlyDevelopmentof MouseTelencephalon.PLoSONE6(8):e23013.doi:10.1371/journal.pone.0023013 Editor:PatrickCallaerts,VIBKatholiekeUniversiteitLeuven,Belgium ReceivedFebruary7,