神经元的迁移ppt课件

1,神经系统的发育,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,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,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,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,6,发育过程中大脑皮层的改变,7,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,8,神经细胞的增殖NeuronalProliferation,9,M,G1,G2,S,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-1011neurons,Onlyafewmonths,10,?,?,?,11,内因说,外因说,12,G1期的时程决定分裂方式,N,neuron;P,precursorcell.,MC,B,A,细胞命运决定因子,13,转录因子决定细胞命运,细胞命运的决定(cellfatedetermination)-Notch-1和numb蛋白的不均匀分布,14,不对称分裂决定细胞命运,1mothercellproduces10,000daughtercells,250，000/minute-1011neurons,Onlyafewmonths,?,15,神经细胞的迁移和分化NeuronalMigrationandProliferation,16,3Hthymidine,DiI,DiO,hydrophilicdye,GFP,Nolabel:C.elegans,Bromodeoxyuridine(BrDu),细胞标记方法,17,特异性表达某种容易检测得到的基因,18,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10thday,Results:,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,19,Shownareentireanteroposteriorextentsofthecerebralcortex.,15thd,11thd,13thd,17thd,20,Inside-Out”GradientofCerebralCortexFormationintheRhesusMonkey,21,-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,22,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,23,InternalTimingMechanism内在时间机制,Thetimeorthenumberofcelldivision,Precursorcells,Developmentalfate,24,CommunityMechanism环境作用机制,Precursorcells,Developmentalfate,Induciblecuesthatchangewithtime,25,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,26,EM:Golgi-stainedfetalmacaquetelencephalon,Radialfibersextendingfromparentcellbodiestothepialsurface,wheretheyterminateinacharacteristicendfoot.,高尔基染色法铬酸盐硝酸银染色法,27,Neuronsmigratealongradialglialcellstotheirfinallayers(3000mm),28,radial-directedcorticalneuronalmigration放射状皮层神经细胞迁移,migration:inside-firstoutside-last,Bielasetal.,2004,29,Radialglialcelldivision放射状神经胶质细胞分裂,30,神经细胞迁移和分化的认识过程,31,神经细胞迁移的舞蹈表演,32,Thearrowspointtothetipoftheleadingprocess.,Initialventricle-directed;Subsequentlytowardsthepialsurface.,33,Twomodesofradialmigration放射性迁移的两种方式,Locomotion,Movementoftheentirecell,includingitsleadingandtrailingprocess,overconsiderabledistance,e.g.,glial-guidedradialmovementofneurons,Translocation,Thecellextendsaleadingprocessinthedirectionofmigration,thenmovesthenucleusthroughtheelongatedprocesstoitsdestination,34,AcelldisplayingsomaltranslocationinanE14corticalslice,Nadarajahetal.,2001,35,Translocatingcellswithbranched,pial-directedprocesses,Nadarajahetal.,2001,36,acelldisplayingpresumptiveglial-guidedlocomotion,37,Bielas,Annu.Rev.CellDev.Biol.2004.20:593618,Thetwodistinctformsofcorticalneuronmovement,38,Non-ratial/tangentialmigration切线性迁移,39,Majorroutesoftangentialmigration,(1)MGEtothedorsaltelencephalon(2)CGEtodorsaltelencephalon(3)Cortical-striatalboundarytotheventrolateraltelencephalon(lateralcorticalstream)(4)LGEtotheolfactorybulb(rostralmigratorystream).,CGE,caudalganglioniceminenceCTX,neocortexLGE,lateralganglioniceminenceMGE,medialganglioniceminenceOB,olfactorybulb,40,knownandhypothesizedroutesoftangentialcellmigration,(1)MGEtoneocortexandhippocampus(2)MGEtoLGE(3)corticalstriatalboundarytoventrolateraltelencephalon(lateralcorticalstream)(4)LGEtoneocortexandhippocampus(5)CGEtodorsaltelencephalon(6)LGEtoolfactorybulb(rostralmigratorystream)(7)Retrobulbarregiontomarginalzone,41,neuronsfromthemedialganglioniceminence(MGE)oftheventraltelencephalonmigratetowardthedorsaltelencephalon.Initially,migrationinthecortexistangentialbutthenbecomesradialorobliqueasneuronsenterthecorticalplate.,42,Cell-cellinteraction,Cell-ECMinteraction,43,Defectsinneuronalmigration,Bielasetal.,2004,分子层,44,Positionofcellsbornatspecificdevelopmentaltimesisinvertedintheadultreelercerebralcortex,45,defectsinneuronalmigration,TissirandGoffinet,2003,46,Theoveralldivisionsofthecerebralwallareobviousinreeler.Butthecorticalplateisdisorganizedandcellsaredisplacedbyfibersthatrunobliquelyinthecerebralwall.ManysubplatecellsarelocatedwiththeCajal-Retziuscellsinarelativelycell-denseregionknownasthesuperplate(spp).,Corticalplateneurons