神经元的迁移课件

神经系统的发育1.神经系统的发育1.本图反应了胚胎神经系统的早期发育过程.a)最初的胚胎中枢神经系统从薄层的外胚层开始发育.b)在神经系统发育中重要的第一步:神经沟的形成;c)神经沟壁,即神经褶向中靠拢并融合,形成神经管;d)随着神经管的生长,部分外胚层内陷到表层下,形成神经嵴,最后发育成外周神经系统.神经管神经嵴体节神经褶神经沟中胚层内胚层神经板复习2.本图反应了胚胎神经系统的早期发育过程.a)最初的胚胎中枢脑的分化神经管前脑中脑后脑视泡端脑泡间脑视神经、视网膜大脑皮层、白质、嗅球丘脑、下丘脑、脑室顶盖---上丘、下丘被盖中脑水管小脑脑桥延髓第四脑室复习3.脑的分化神经管前脑中脑后脑视泡端脑泡间脑视神经、视网膜大脑皮大脑皮层的形态新皮层嗅皮层海马嗅裂侧脑室哺乳动物的三种皮层新皮层Neocortex，仅存于哺乳动物嗅皮层Olfactorycortex海马Hippocampus嗅裂Rhinalfissure侧脑室Lateralventricle旧皮层或古皮层4.大脑皮层的形态新皮层嗅皮层海马嗅裂侧脑室哺乳动物的三种皮层新皮层神经元都是呈层状排列的，而且绝大部分神经元胞体与脑的表面平行。分子层:最靠近表面的神经细胞层,由一层无神经元的组织将皮层与软脑膜分隔开。各层至少都有一层细胞，伸出大量的称为顶树突的树突，这些顶树突会伸入到第一层，在那里形成众多的分叉。大脑皮层的细胞结构

分子层Molecularlayer软脑膜Pialsurface顶树突Apicaldentrite短吻鳄大鼠5.皮层神经元都是呈层状排列的，而且绝大部分神经元胞体与脑的表面发育过程中大脑皮层的改变6.发育过程中大脑皮层的改变6.神经细胞的增殖Neuronalproliferation神经细胞的迁移Neuronalmigration神经细胞分化Neuraldifferentiation轴突伸展Axonguidance突触形成Synaptogenesis神经细胞的死亡Neuronaldeath大脑皮层的形成7.神经细胞的增殖Neuronalproliferation神经细胞的增殖

NeuronalProliferation8.神经细胞的增殖8.MG1G2S神经细胞增殖的舞蹈表演室层边缘层脑室侧软膜侧囊泡壁250，000perminute------------------------1011neuronsOnlyafewmonths9.MG1G2S神经细胞增殖的舞蹈表演室层边缘层脑室侧软膜侧囊泡???10.???10.内因说外因说11.内因说外因说11.G1期的时程决定分裂方式N,neuron;P,precursorcell.MCBA细胞命运决定因子12.G1期的时程决定分裂方式N,neuron;MCBA细胞转录因子决定细胞命运细胞命运的决定(cell–fatedetermination)---------Notch-1和numb蛋白的不均匀分布

13.转录因子决定细胞命运细胞命运的决定(cell–fated不对称分裂决定细胞命运1mothercellproduces≈10,000daughtercells250，000/minute------------------------1011neuronsOnlyafewmonths?14.不对称分裂决定细胞命运1mothercellprodu神经细胞的迁移和分化NeuronalMigrationandProliferation15.神经细胞的迁移和分化15.[3H]thymidineDiI,DiO,hydrophilicdyeGFPNolabel:C.elegansBromodeoxyuridine(BrDu)细胞标记方法16.[3H]thymidineDiI,DiO,hydroph特异性表达某种容易检测得到的基因17.特异性表达某种容易检测得到的基因17.J.B.Angevine,etal..Nature192:766-768,1961注射:妊娠11th,13th,15th,or17thdays检测:注射后1hror出生后10thdayResults:Methods:Conclusion1:皮层细胞主要来源于侧脑室室管膜。注射后1hr检测:

细胞位于室管膜附近。神经细胞迁移的证据18.J.B.Angevine,etal..NatureShownareentireanteroposteriorextentsofthecerebralcortex.15thd11thd13thd17thdNeuronsmigrate.2.Latergenerationsof postmitoticneurons migrateoutbeyond earliercellsConclusions19.ShownareentireanteroposteriInside-Out”GradientofCerebralCortexFormationintheRhesusMonkey20.Inside-Out”GradientofCerebr-

Inside-out较早分化的较大神经元先迁移并形成最内层，依次顺序向外；而较晚分化的较小神经元则通过已形成的层次迁移并形成其外侧新的层次；不论皮质的什么区域，其最内层总是最早分化，而最外层则最后分化。边缘层室层放射状胶质细胞突起21.-Inside-out较早分化的较大神经元先迁移r:rodcell杆状双核细胞t:terminalofarodcellbp:bipolarcell两极(神经)细胞mg：glialcell神经胶质细胞22.22.InternalTimingMechanism内在时间机制ThetimeorthenumberofcelldivisionPrecursorcellsDevelopmentalfate23.InternalTimingMechanismThetCommunityMechanism环境作用机制PrecursorcellsDevelopmentalfateInduciblecuesthatchangewithtime24.CommunityMechanismPrecursorc神经元迁移的方式根据神经元迁移的方向：放射性迁移：radialmigration

切线性迁移：tangentialmigration

25.神经元迁移的方式根据神经元迁移的方向：25.EM:Golgi-stainedfetalmacaquetelencephalonRadialfibersextendingfromparentcellbodiestothepialsurface,wheretheyterminateinacharacteristicendfoot.高尔基染色法－铬酸盐－硝酸银染色法26.EM:Golgi-stainedfetalmacaquNeuronsmigratealongradialglialcellstotheirfinallayers(3000mm)27.Neuronsmigratealongradialgradial-directedcorticalneuronalmigration

放射状皮层神经细胞迁移migration:inside-firstoutside-lastBielasetal.,200428.radial-directedcorticalneuroRadialglialcelldivision放射状神经胶质细胞分裂29.Radialglialcelldivision29.神经细胞迁移和分化的认识过程30.神经细胞迁移和分化的认识过程30.神经细胞迁移的舞蹈表演31.神经细胞迁移的舞蹈表演31.Thearrowspointtothetipoftheleadingprocess.Initialventricle-directed;Subsequentlytowardsthepialsurface.32.ThearrowspointtothetipofTwomodesofradialmigration放射性迁移的两种方式LocomotionMovementoftheentirecell,includingitsleadingandtrailingprocess,overconsiderabledistancee.g.,glial-guidedradialmovementofneuronsTranslocationThecellextendsaleadingprocessinthedirectionofmigration,thenmovesthenucleusthroughtheelongatedprocesstoitsdestination33.TwomodesofradialmigrationLAcelldisplayingsomaltranslocationinanE14corticalsliceNadarajahetal.,200134.AcelldisplayingsomaltranslTranslocatingcellswithbranched,pial-directedprocessesNadarajahetal.,200135.Translocatingcellswithbranc

acelldisplayingpresumptiveglial-guidedlocomotion36.

Bielas,Annu.Rev.CellDev.Biol.2004.20:593–618Thetwodistinctformsofcorticalneuronmovement37.Bielas,Annu.Rev.CellDev.BNon-ratial/tangentialmigration切线性迁移38.Non-ratial/tangentialmigratioMajorroutesoftangentialmigration(1)MGEtothedorsaltelencephalon(2)CGEtodorsaltelencephalon(3)Cortical-striatalboundarytotheventrolateraltelencephalon(lateralcorticalstream)(4)LGEtotheolfactorybulb(rostralmigratorystream).CGE,caudalganglioniceminenceCTX,neocortexLGE,lateralganglioniceminenceMGE,medialganglioniceminenceOB,olfactorybulb39.Majorroutesoftangentialmigknownandhypothesizedroutesoftangentialcellmigration(1)MGEtoneocortexandhippocampus(2)MGEtoLGE(3)cortical–striatalboundaryto ventrolateraltelencephalon (lateralcorticalstream)(4)LGEtoneocortexandhippocampus(5)CGEtodorsaltelencephalon(6)LGEtoolfactorybulb (rostralmigratorystream)(7)Retrobulbarregiontomarginalzone40.knownandhypothesizedroutesneuronsfromthemedialganglioniceminence(MGE)oftheventraltelencephalonmigratetowardthedorsaltelencephalon.Initially,migrationinthecortexistangentialbutthenbecomesradialorobliqueasneuronsenterthecorticalplate.41.neuronsfromthemedialgangliCell-cellinteractionCell-ECMinteraction42.Cell-cellinteractionCell-ECMDefectsinneuronalmigrationBielasetal.,2004分子层43.DefectsinneuronalmigrationBPositionofcellsbornatspecificdevelopmentaltimesisinvertedintheadultreelercerebralcortex44.PositionofcellsbornatspecdefectsinneuronalmigrationTissirandGoffinet,200345.defectsinneuronalmigrationTTheoveralldivisionsofthecerebralwallareobviousinreeler.Butthecorticalplateisdisorganizedandcellsaredisplacedbyfibersthatrunobliquelyinthecerebralwall.ManysubplatecellsarelocatedwiththeCajal-Retziuscellsinarelativelycell-denseregionknownasthesuperplate(spp).Corticalplateneurons(gray)positionsbetweentheCajal-Retziuscells(black)thatproduceReelin(stipples)andthesubplatelayer.Corticalplateneuronsfailstomigratepastthesubplateandinsteadaccumulatesinadisorganizedfashioninthesuperplate.46.Theoveralldivisionsofthec思考题1、神经元迁移的形式2、神经元细胞放射性迁移的两种方式47.思考题1、神经元迁移的形式47.神经系统的发育48.神经系统的发育1.本图反应了胚胎神经系统的早期发育过程.a)最初的胚胎中枢神经系统从薄层的外胚层开始发育.b)在神经系统发育中重要的第一步:神经沟的形成;c)神经沟壁,即神经褶向中靠拢并融合,形成神经管;d)随着神经管的生长,部分外胚层内陷到表层下,形成神经嵴,最后发育成外周神经系统.神经管神经嵴体节神经褶神经沟中胚层内胚层神经板复习49.本图反应了胚胎神经系统的早期发育过程.a)最初的胚胎中枢脑的分化神经管前脑中脑后脑视泡端脑泡间脑视神经、视网膜大脑皮层、白质、嗅球丘脑、下丘脑、脑室顶盖---上丘、下丘被盖中脑水管小脑脑桥延髓第四脑室复习50.脑的分化神经管前脑中脑后脑视泡端脑泡间脑视神经、视网膜大脑皮大脑皮层的形态新皮层嗅皮层海马嗅裂侧脑室哺乳动物的三种皮层新皮层Neocortex，仅存于哺乳动物嗅皮层Olfactorycortex海马Hippocampus嗅裂Rhinalfissure侧脑室Lateralventricle旧皮层或古皮层51.大脑皮层的形态新皮层嗅皮层海马嗅裂侧脑室哺乳动物的三种皮层新皮层神经元都是呈层状排列的，而且绝大部分神经元胞体与脑的表面平行。分子层:最靠近表面的神经细胞层,由一层无神经元的组织将皮层与软脑膜分隔开。各层至少都有一层细胞，伸出大量的称为顶树突的树突，这些顶树突会伸入到第一层，在那里形成众多的分叉。大脑皮层的细胞结构

分子层Molecularlayer软脑膜Pialsurface顶树突Apicaldentrite短吻鳄大鼠52.皮层神经元都是呈层状排列的，而且绝大部分神经元胞体与脑的表面发育过程中大脑皮层的改变53.发育过程中大脑皮层的改变6.神经细胞的增殖Neuronalproliferation神经细胞的迁移Neuronalmigration神经细胞分化Neuraldifferentiation轴突伸展Axonguidance突触形成Synaptogenesis神经细胞的死亡Neuronaldeath大脑皮层的形成54.神经细胞的增殖Neuronalproliferation神经细胞的增殖

NeuronalProliferation55.神经细胞的增殖8.MG1G2S神经细胞增殖的舞蹈表演室层边缘层脑室侧软膜侧囊泡壁250，000perminute------------------------1011neuronsOnlyafewmonths56.MG1G2S神经细胞增殖的舞蹈表演室层边缘层脑室侧软膜侧囊泡???57.???10.内因说外因说58.内因说外因说11.G1期的时程决定分裂方式N,neuron;P,precursorcell.MCBA细胞命运决定因子59.G1期的时程决定分裂方式N,neuron;MCBA细胞转录因子决定细胞命运细胞命运的决定(cell–fatedetermination)---------Notch-1和numb蛋白的不均匀分布

60.转录因子决定细胞命运细胞命运的决定(cell–fated不对称分裂决定细胞命运1mothercellproduces≈10,000daughtercells250，000/minute------------------------1011neuronsOnlyafewmonths?61.不对称分裂决定细胞命运1mothercellprodu神经细胞的迁移和分化NeuronalMigrationandProliferation62.神经细胞的迁移和分化15.[3H]thymidineDiI,DiO,hydrophilicdyeGFPNolabel:C.elegansBromodeoxyuridine(BrDu)细胞标记方法63.[3H]thymidineDiI,DiO,hydroph特异性表达某种容易检测得到的基因64.特异性表达某种容易检测得到的基因17.J.B.Angevine,etal..Nature192:766-768,1961注射:妊娠11th,13th,15th,or17thdays检测:注射后1hror出生后10thdayResults:Methods:Conclusion1:皮层细胞主要来源于侧脑室室管膜。注射后1hr检测:

细胞位于室管膜附近。神经细胞迁移的证据65.J.B.Angevine,etal..NatureShownareentireanteroposteriorextentsofthecerebralcortex.15thd11thd13thd17thdNeuronsmigrate.2.Latergenerationsof postmitoticneurons migrateoutbeyond earliercellsConclusions66.ShownareentireanteroposteriInside-Out”GradientofCerebralCortexFormationintheRhesusMonkey67.Inside-Out”GradientofCerebr-

Inside-out较早分化的较大神经元先迁移并形成最内层，依次顺序向外；而较晚分化的较小神经元则通过已形成的层次迁移并形成其外侧新的层次；不论皮质的什么区域，其最内层总是最早分化，而最外层则最后分化。边缘层室层放射状胶质细胞突起68.-Inside-out较早分化的较大神经元先迁移r:rodcell杆状双核细胞t:terminalofarodcellbp:bipolarcell两极(神经)细胞mg：glialcell神经胶质细胞69.22.InternalTimingMechanism内在时间机制ThetimeorthenumberofcelldivisionPrecursorcellsDevelopmentalfate70.InternalTimingMechanismThetCommunityMechanism环境作用机制PrecursorcellsDevelopmentalfateInduciblecuesthatchangewithtime71.CommunityMechanismPrecursorc神经元迁移的方式根据神经元迁移的方向：放射性迁移：radialmigration

切线性迁移：tangentialmigration

72.神经元迁移的方式根据神经元迁移的方向：25.EM:Golgi-stainedfetalmacaquetelencephalonRadialfibersextendingfromparentcellbodiestothepialsurface,wheretheyterminateinacharacteristicendfoot.高尔基染色法－铬酸盐－硝酸银染色法73.EM:Golgi-stainedfetalmacaquNeuronsmigratealongradialglialcellstotheirfinallayers(3000mm)74.Neuronsmigratealongradialgradial-directedcorticalneuronalmigration

放射状皮层神经细胞迁移migration:inside-firstoutside-lastBielasetal.,200475.radial-directedcorticalneuroRadialglialcelldivision放射状神经胶质细胞分裂76.Radialglialcelldivision29.神经细胞迁移和分化的认识过程77.神经细胞迁移和分化的认识过程30.神经细胞迁移的舞蹈表演78.神经细胞迁移的舞蹈表演31.Thearrowspointtothetipoftheleadingprocess.Initialventricle-directed;Subsequentlytowardsthepialsurface.79.ThearrowspointtothetipofTwomodesofradialmigration放射性迁移的两种方式LocomotionMovementoftheentirecell,includingitsleadingandtrailingprocess,overconsiderabledistancee.g.,glial-guidedradialmovementofneuronsTranslocationThecellextendsaleadingprocessinthedirectionofmigration,thenmovesthenucleusthroughtheelongatedprocesstoitsdestination80.TwomodesofradialmigrationLAcelldisplayingsomaltranslocationinanE14corticalsliceNadarajahetal.,200181.AcelldisplayingsomaltranslTranslocatingcellswithbranched,pial-directedprocessesNadarajahetal.,200182.Translocatingcellswithbranc

acelldisplayingpresumptiveglial-guidedlocomotion83.

Bielas,Annu.Rev.CellDev.Biol.2004.20:593–618Thetwodistinctformsofcorticalneuronmovement84.Bielas,Annu.Rev.CellDev.BNon-ratial/tangentialmigration切线性迁移85.Non-ratial/tangentialmigratioMajorroutesoftangentialmigration(1)MGEtothedorsaltelencephalon(2)CGEtodorsaltelencephalon(3)Cortical-striatalboundarytotheventrolateraltelencephalon(lateralcorticalstream)(4)LGEtotheolfactorybulb(rostralmigratorystream).CGE,caudalganglioniceminenceCTX,neocortexLGE,lateralganglioniceminenceMGE,medialganglioniceminenceOB,olfactorybulb86.Majorroutesoftangentialmigknownandhypothesizedroutesoftangentialcellmigration(1)MGEtoneocortexandhippocampus(2)MGEtoLGE(3)cortical–striatalboundaryto ventrolateraltelencephalon (lateralcorticalstream)(4)LGEtoneocortexandhippocampus(5)CGEtodorsaltelencephalon(6)LGEtoolfactorybulb (rostralmigratorystr