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脑的分化神神经经管管前脑前脑中脑中脑后脑后脑视泡视泡端脑泡端脑泡间脑间脑视神经、视网膜视神经、视网膜大脑皮层、白质、嗅球大脑皮层、白质、嗅球丘脑、下丘脑、脑室丘脑、下丘脑、脑室顶盖顶盖-上丘、下丘上丘、下丘被盖被盖中脑水管中脑水管小脑小脑脑桥脑桥延髓延髓第四脑室第四脑室复习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新皮层嗅皮层嗅皮层海马海马嗅裂嗅裂侧脑室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6.1.神经细胞的增殖神经细胞的增殖 Neuronal proliferation2.神经细胞的迁移神经细胞的迁移 Neuronal migration3.神经细胞分化神经细胞分化 Neural differentiation4.轴突伸展轴突伸展 Axon guidance5.突触形成突触形成 Synaptogenesis6.神经细胞的死亡神经细胞的死亡 Neuronal death大脑皮层的形成7.神经细胞的增殖Neuronalproliferation神经细胞的增殖神经细胞的增殖 Neuronal Proliferation8.神经细胞的增殖8.MG1G2S神经细胞增殖的舞蹈表演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250，000 per minute -1011 neuronsOnly a few months9.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.内因说内因说外因说外因说11.内因说外因说11.G1 期的时程决定分裂方式期的时程决定分裂方式N,neuron;P,precursorcell.MCBA细胞命运决定因子细胞命运决定因子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 fate determination)-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(cellfated不对称分裂决定细胞命运不对称分裂决定细胞命运1 mother cell produces 10,000 daughter cells250，000/minute -1011 neuronsOnly a few months?14.不对称分裂决定细胞命运1mothercellprodu神经细胞的迁移和分化神经细胞的迁移和分化Neuronal Migration and Proliferation15.神经细胞的迁移和分化15.3HthymidineDiI,DiO,hydrophilic dyeGFPNo label:C.elegansBromodeoxyuridine(BrDu)细胞标记方法16.3HthymidineDiI,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,et al.Nature 192:766-768,1961 注射注射:妊娠妊娠11th,13th,15th,or 17th days 检测检测:注射后注射后1 hr or 出生后出生后10th dayResults:Methods:Conclusion 1:皮层细胞主要来源于侧脑室室管膜。皮层细胞主要来源于侧脑室室管膜。注射后注射后1 hr检测检测:细胞位于室管膜附近。细胞位于室管膜附近。神经细胞迁移的证据18.J.B.Angevine,etal.NatureShown are entire anteroposterior extents of the cerebral cortex.15th d11th d13th d17th d1.Neurons migrate.2.Later generations of postmitotic neurons migrate out beyond earlier cellsConclusions19.ShownareentireanteroposteriInside-Out”Gradient of Cerebral Cortex Formation in the Rhesus Monkey20.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；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。的什么区域，其最内层总是最早分化，而最外层则最后分化。边缘层边缘层室层室层放射状胶质细胞放射状胶质细胞突起突起21.-Inside-out较早分化的较大神经元先迁移r:rod cell 杆状双核细胞t:terminal of a rod cellbp:bipolar cell两极(神经)细胞mg：glial cell神经胶质细胞22.22.Internal Timing Mechanism内在时间机制The time or the number of cell division Precursor cellsDevelopmental fate 23.InternalTimingMechanismThetCommunity Mechanism环境作用机制Precursor cellsDevelopmental fate Inducible cues that change with time24.CommunityMechanismPrecursorc神经元迁移的方式根据神经元迁移的方向：放射性迁移：radial migration切线性迁移：tangential migration25.神经元迁移的方式根据神经元迁移的方向：25.EM:Golgi-stained fetal macaque telencephalonRadial fibers extending from parent cell bodies to the pial surface,where they terminate in a characteristic endfoot.高尔基染色法高尔基染色法铬酸盐硝酸银染色法26.EM:Golgi-stainedfetalmacaquNeurons migrate along radial glial cells to their final layers(3000 m mm)27.Neuronsmigratealongradialgradial-directedcorticalneuronalmigration放射状皮层神经细胞迁移migration:inside-firstoutside-lastBielas et al.,200428.radial-directedcorticalneuroRadial glial cell division放射状神经胶质细胞分裂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.Initial ventricle-directed;Subsequently towards the pial surface.32.ThearrowspointtothetipofTwo modes of radial migration放射性迁移的两种方式LocomotionMovement of the entire cell,including its leadingand trailing process,over considerable distancee.g.,glial-guided radial movement of neuronsTranslocationThe cell extends a leading process in the direction of migration,then moves the nucleus throughthe elongated process to its destination33.TwomodesofradialmigrationLA cell displaying somal translocation in an E14 cortical sliceNadarajah et al.,200134.AcelldisplayingsomaltranslTranslocating cells with branched,pial-directed processesNadarajah et al.,200135.Translocatingcellswithbranca cell displaying presumptive glial-guided locomotion36.Bielas,Annu.Rev.Cell Dev.Biol.2004.20:593618The two distinct forms of cortical neuron movement37.Bielas,Annu.Rev.CellDev.BNon-ratial/tangential migration切线性迁移切线性迁移38.Non-ratial/tangentialmigratioMajor routes of tangential migration(1)MGE to the dorsal telencephalon(2)CGE to dorsal telencephalon(3)Cortical-striatal boundary to the ventrolateral telencephalon(lateral cortical stream)(4)LGE to the olfactory bulb(rostral migratory stream).CGE,caudalganglioniceminenceCTX,neocortexLGE,lateralganglioniceminenceMGE,medialganglioniceminenceOB,olfactorybulb39.Majorroutesoftangentialmigknown and hypothesized routes of tangential cell migration(1)MGE to neocortex and hippocampus(2)MGE to LGE(3)corticalstriatal boundary to ventrolateral telencephalon(lateral cortical stream)(4)LGE to neocortex and hippocampus(5)CGE to dorsal telencephalon(6)LGE to olfactory bulb(rostral migratory stream)(7)Retrobulbar region to marginal zone40.knownandhypothesizedroutesneurons from the medial ganglionic eminence(MGE)of the ventral telencephalon migrate toward the dorsal telencephalon.Initially,migration in the cortex is tangential but then becomes radial or oblique as neurons enter the cortical plate.41.neuronsfromthemedialgangliCell-cell interactionCell-ECM interaction42.Cell-cellinteractionCell-ECMDefectsinneuronalmigrationBielas et al.,2004分子层43.DefectsinneuronalmigrationBPosition of cells born at specific developmental times is inverted in the adult reeler cerebral cortex44.PositionofcellsbornatspecdefectsinneuronalmigrationTissir and Goffinet,200345.defectsinneuronalmigrationTThe overall divisions of the cerebral wall are obvious in reeler.But the cortical plate is disorganized and cells are displaced by fibers that run obliquely in the cerebral wall.Many subplate cells are located with the Cajal-Retzius cells in a relatively cell-dense region known as the superplate(spp).Cortical plate neurons(gray)positions between the Cajal-Retzius cells(black)that produce Reelin(stipples)and the subplate layer.Cortical plate neurons fails to migrate past the subplate and instead accumulates in a disorganized fashion in the superplate.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.