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2016322272~276ChineseJournalofNeuroanatomy10YZ53J50301*021-51322146E-mailyan2007h@hotmail.com,*201203【】DOI10.16557/j.cnki.1000-7547.2016.02.023neuralstemcellsNSCssubgranularzoneSGZsubventracularzoneSVZ。NSCstransi-entamplifyingprogenitorsTAPs、1。NSCs、。NSCs、“”WntNotchSonichedgehogShhTGF-β2。1WntWntβ-cateninβ-cateninWntWnt1、Wnt3a、Wnt10、Wnt8aWnt4、Wnt5a、Wnt5b、Wnt7a3。Wntβ-catenin、Ax-in、APC、GSK-3ββ-cateninβ-TrCPβ-cateninWntFzdLRP5/6WntGSK-3ββ-cateninTCF/LEFCyclinD1、Ngn-1、Ngn-24。Qu5Wnt7aNSCsNSCsNSCs。Wnt7a-/-dentategyrusDGNSCsNSCs。Wnt7aNSCs“”1Wnt7a/β-catenin-cy-clinD1G1NSCs2Wnt7a/β-catenin-Ngn2NSCs、。Wnt7aNSCs、。Wnt7aNgn1mRNAFGFNSCs6。β-cateninWntWnt/PCP。ATP2ATPasetransportinglysosomalaccessoryprotein2ATP6AP2WntWnt、Fzd、LRP5/6。adulthippocampalprogenitorcellsAHPSWntLRP6、Fzd4ATP6AP2。Wnt/PCPFzd3Fzd6PCPCelsr1-3mRNANSCsFzd3Celsr1-3Wnt/PCPAHPS7。Wnt3aβ-cateninAHPSAHPSWnt3aTcf/Lef。Wnt5aAHPSWnt/PCPc-JunAHPSWnt/PCP。Wnt5aWnt3aAHPSWnt5aWnt/PCPNSCsWnt3aWnt/β-cateninNSCs、8。WntNotch“”NotchHes1Hes5Mash1NSCsHes5Wnt3aMash1NSCsNotchWnt3aWntHes5Wnt3a9。Wnt/β-cateninSVZdorsalSVZdSVZGSK3βNSCsNSCs10dSVZWnt3a11。AnderssonER12Wnt1Lmx1aMash1Ngn2Wnt1。Wnt5a-/-/Wnt1-/-Nurr1+Wnt1Wnt5a“”Wnt1Wnt5aWnt5aWnt1。NSCsWnt13。WntWnt14。WntNSCsNSCs“”15。2NotchNotchNSCs、。NotchNotchNotch1-4Jagged1Jagged2Dll1-4CBF/CSL。NotchTACEPS1γ-NICDRBP-JkRAMNICDbHLHHes1、Hes516。Notch“”NSCsNSCs9。NotchNSCsNotch1718。Shimojo1920Hes1。Hes1NSCsNSCsHes1Ngn2Dll1。Ngn2Dll1NotchHes1NSCsNgn2Hes1NSCs。Notch1mRNAHes1NSCsDll1、NICDHes1NSCsHes1DGNSCs21-23NSCs“”。NotchSVZ。Imayoshi24Notch1NSCsRBJkNSCsNSCs。BasakO25NSCsSVZNotch1。Notch1NSCsTAPsNotch1NSCsRBJkNSCsRBJkNSCs。γAPPLRP2ErbB4NICDNSCs“”NICDNotch26。NotchNSCsNSCs。3SonicHedgehogShhHedgehogSHHDHHIHHDhh、IhhShhHedgehogPtcSmoPatchedSmoth-enedPtcShhSmoShh。HedgehogPtcPtcSmoSmoGliGli2Gli2AGli2AGli1Gli1Gli1Shh。ShhGli2Gli3Gli3Gli3Gli3RShh27。Shh、、。SVZSGZShhPtc、SmoShhShhSmoSVZSGZDGNSCs2。Balordi28HedgehogHedgehog-/-7dSVZNSCsTAPs30dShhNSCsTAPs372“iche”。BambakidisNC29ShhGli1NSCsSVZNestin+。Shh“iche”NSCs、、30。SmoNSCsNSCsGli2Gli3RGFAPGli3RNSCs3132。ShhGli3RNSCs。NSCsShh33。SVZNSCsGli3Rgp130gp130IL-6CNTF、IL-6、LIFCT-1。Gli3Rgp130JAK-STAT3GFAP+。Gli3NumbNumbvascularcelladhesionmoleculeVCAME-E-cadherinVCAMGli3NSCs3435。Gli3“iche”。4TGF-β/BMPTGFββtransforminggrowthfactor-βTGF-β、activin、bonemorphogeneticproteinBMP、in-hibins、。TGF-βⅠTGF-βRⅠ、ⅡTGF-βRⅡ、ⅢTGF-βRⅢ。TGF-βRⅡTGF-βRⅠTGF-βRⅠ36。SmadTGF-β/BMPTGF-βRⅠ3R-SmadsCo-SmadsI-Smads37。“”。38。DiasJM39TGF-β“”。TGF-β。TGF-βNSCsNSCs。TGF-βRIINSCsFGFWntFGF8Wnt1TGF-βFGFWnt40。TKandasamyM41TGF-β1NSCsNotchHes1Dll1Jagged1Mash1NSCs、MBPNSCsSmad2。“niche”TGF-β1NSCs、。BMP20TGFβ、2。SGZBMP4NSCs42。SVZBMPNogginBMPSVZNSCsSGZNogginmRNAFXR2FXR2NogginBMPNSCs43。BMP。RadialglialcellsRGNSCsTGF-β1RRGRGNSCs44。TGF-β、、、45。。NSCsWntNotchTGF-β/BMPShh“cross-talk”。Smad3NICDCBFHes1DNABMP2Smad1NICDHes5Hesr1NSC4647。TGF-β/Smad3Gli2Gli1TIEG-1Gli1N-myc48。Notch47220163322Ptc1SmoGliNSCsShh49。WntNotchNSCs。NotchWntNumbβ-cateninWntDshNotchCSLNICD/CSL/MAMLβ-cateninP300P/CAFNotch/RBP-Jk50-52。NSCs“”、。NSCs、、、“cross-talk”“”。NSCs、、。1ChristieKJTurnleyAM.Regulationofendogenousneuralstem/progenitorcellsforneuralrepair-factorsthatpromoteneurogenesisandgliogenesisinthenormalanddamagedbrainJ.FrontCellNeurosci2012670-71.2FaigleRSongH.SignalingmechanismsregulatingadultneuralstemcellsandneurogenesisJ.BiochimBiophysActa201318302435-2448.3.WntJ.2013121177-11794VanCampJKBeckersSZegersDetal.WntsignalingandthecontrolofhumanstemcellfateJ.StemCellRev201410207-229.5QuQSunGMuraiKetal.Wnt7aRegulatesMultipleStepsofNeurogenesisJ.CellMolBiol2013332551-2559.6HirabayashiYItohYTabataHetal.TheWnt/beta-cateninpathwaydirectsneuronaldifferentiationofcorticalneuralprecursorcellsJ.Development20041312791-2801.7SchaferSTHanJPenaMetal.TheWntadaptorproteinATP6AP2regulatesmultiplestagesofadulthippocampalneurogene-sisJ.JNeurosci2015354983-4998.8DavidsonKCJamshidiPDalyRetal.Wnt3aregulatessurvivalexpansionandmaintenanceofneuralprogenitorsderivedfromhu-manembryonicstemcellsJ.MolCellNeurosci200736408-415.9MussmannCHubnerRTrilckMetal.HES5IsaKeyMediatorofWnt-3a-InducedNeuronalDifferentiationJ.StemCellsDev2014231328-1339.10AzimKRiveraARatneteauOetal.GSK3betaregulatesoligo-dendrogenesisinthedorsalmicrodomainofthesubventricularzoneviaWnt-beta-cateninsignalingJ.Glia201462778-779.11OrtegaFGascónSMasserdottiGetal.Oligodendrogliogenicandneurogenicadultsubependymalzoneneuralstemcellsconsti-tutedistinctlineagesandexhibitdifferentialresponsivenesstoWntsignallingJ.NatCellBiol201315602-613.11OrtegaFGascónSMasserdottiGetal.OligodendrogliogenicandneurogenicadultsubependymalzoneneuralstemcellsconstitutedistinctlineagesandexhibitdifferentialresponsivenesstoWntsig-nallingJ.NatCellBiol201315602-613.12AnderssonERSaltoCVillaescusaJCetal.Wnt5acooperateswithcanonicalWntstogeneratemidbraindopaminergicneuronsinvivoandinstemcellsJ.ProcNatlAcadSciUSA2013110602-610.13CrowtherAJSongJ.Activity-dependentsignalingmechanismsreg-ulatingadulthippocampalneuralstemcellsandtheirprogenyJ.NeurosciBull201430542-556.14PiccinDMorsheadCM.Wnt
本文标题:神经干细胞增殖与分化的主要调控信号通路研究进展-杨仁松
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