神经元的分化课件

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

NeuronalProliferation8???10G1期的时程决定分裂方式N,neuron;P,precursorcell.MCBA细胞命运决定因子12不对称分裂决定细胞命运1mothercellproduces≈10,000daughtercells250，000/minute------------------------1011neuronsOnlyafewmonths?14神经细胞的迁移和分化NeuronalMigrationandProliferation15[3H]thymidineDiI,DiO,hydrophilicdyeGFPNolabel:C.elegansBromodeoxyuridine(BrDu)细胞标记方法16特异性表达某种容易检测得到的基因17J.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18Inside-Out”GradientofCerebralCortexFormationintheRhesusMonkey20-

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21InternalTimingMechanism内在时间机制ThetimeorthenumberofcelldivisionPrecursorcellsDevelopmentalfate23CommunityMechanism环境作用机制PrecursorcellsDevelopmentalfateInduciblecuesthatchangewithtime24EM:Golgi-stainedfetalmacaquetelencephalonRadialfibersextendingfromparentcellbodiestothepialsurface,wheretheyterminateinacharacteristicendfoot.高尔基染色法－铬酸盐－硝酸银染色法26Neuronsmigratealongradialglialcellstotheirfinallayers(3000mm)27radial-directedcorticalneuronalmigration

放射状皮层神经细胞迁移migration:inside-firstoutside-lastBielasetal.,200428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31Thearrowspointtothetipoftheleadingprocess.Initialventricle-directed;Subsequentlytowardsthepialsurface.32Twomodesofradialmigration放射性迁移的两种方式LocomotionMovementoftheentirecell,includingitsleadingandtrailingprocess,overconsiderabledistancee.g.,glial-guidedradialmovementofneuronsTranslocationThecellextendsaleadingprocessinthedirectionofmigration,thenmovesthenucleusthroughtheelongatedprocesstoitsdestination33AcelldisplayingsomaltranslocationinanE14corticalsliceNadarajahetal.,200134Translocatingcellswithbranched,pial-directedprocessesNadarajahetal.,200135

acelldisplayingpresumptiveglial-guidedlocomotion36Bielas,Annu.Rev.CellDev.Biol.2004.20:593–618Thetwodistinctformsofcorticalneuronmovement37Non-ratial/tangentialmigration切线性迁移38Majorroutesoftangentialmigration(1)MGEtothedorsaltelencephalon(2)CGEtodorsaltelencephalon(3)Cortical-striatalboundarytotheventrolateraltelencephalon(lateralcorticalstream)(4)LGEtotheolfactorybulb(rostralmigratorystream).CGE,caudalganglioniceminenceCTX,neocortexLGE,lateralganglioniceminenceMGE,medialganglioniceminenceOB,olfactorybulb39knownandhypothesizedroutesoftangentialcellmigration(1)MGEtoneocortexandhippocampus(2)MGEtoLGE(3)cortical–striatalboundaryto ventrolateraltelencephalon (lateralcorticalstream)(4)LGEtoneocortexandhippocampus(5)CGEtodorsaltelencephalon(6)LGEtoolfactorybulb (rostralmigratorystream)(7)Retrobulbarregiontomarginalzone40neuronsfromthemedialganglioniceminence(MGE)oftheventraltelencephalonmigratetowardthedorsaltelencephalon.Initially,migrationinthecortexistangentialbutthenbecomesradialorobliqueasneuronsenterthecorticalplate.41Cell-cellinteractionCell-ECMinteraction42DefectsinneuronalmigrationBielasetal.,2004分子层43Positionofcellsbornatspecificdevelopmentaltimesisinvertedintheadultreelercerebralcortex44defectsinneuronalmigrationTissirandGoffinet,200345Theoveralldivisionsofthecerebralwallareobviousinreeler.Butthecorticalplateisdisorganizedandcellsaredisplacedbyfibersthatrunobliquelyinthecerebralwall.ManysubplatecellsarelocatedwiththeCajal-Retziuscellsinarelativelycell-denseregionknownasthesuperplate(spp).Corticalplateneurons(gray)positionsbetweentheCajal