神經(jīng)元的遷移課件

神經(jīng)系統(tǒng)的發(fā)育1.神經(jīng)系統(tǒng)的發(fā)育1.本圖反應(yīng)了胚胎神經(jīng)系統(tǒng)的早期發(fā)育過程.a)最初的胚胎中樞神經(jīng)系統(tǒng)從薄層的外胚層開始發(fā)育.b)在神經(jīng)系統(tǒng)發(fā)育中重要的第一步:神經(jīng)溝的形成;c)神經(jīng)溝壁,即神經(jīng)褶向中靠攏并融合,形成神經(jīng)管;d)隨著神經(jīng)管的生長,部分外胚層內(nèi)陷到表層下,形成神經(jīng)嵴,最后發(fā)育成外周神經(jīng)系統(tǒng).神經(jīng)管神經(jīng)嵴體節(jié)神經(jīng)褶神經(jīng)溝中胚層內(nèi)胚層神經(jīng)板復(fù)習(xí)2.本圖反應(yīng)了胚胎神經(jīng)系統(tǒng)的早期發(fā)育過程.a)最初的胚胎中樞腦的分化神經(jīng)管前腦中腦后腦視泡端腦泡間腦視神經(jīng)、視網(wǎng)膜大腦皮層、白質(zhì)、嗅球丘腦、下丘腦、腦室頂蓋---上丘、下丘被蓋中腦水管小腦腦橋延髓第四腦室復(fù)習(xí)3.腦的分化神經(jīng)管前腦中腦后腦視泡端腦泡間腦視神經(jīng)、視網(wǎng)膜大腦皮大腦皮層的形態(tài)新皮層嗅皮層海馬嗅裂側(cè)腦室哺乳動(dòng)物的三種皮層新皮層Neocortex，僅存于哺乳動(dòng)物嗅皮層Olfactorycortex海馬Hippocampus嗅裂Rhinalfissure側(cè)腦室Lateralventricle舊皮層或古皮層4.大腦皮層的形態(tài)新皮層嗅皮層海馬嗅裂側(cè)腦室哺乳動(dòng)物的三種皮層新皮層神經(jīng)元都是呈層狀排列的，而且絕大部分神經(jīng)元胞體與腦的表面平行。分子層:最靠近表面的神經(jīng)細(xì)胞層,由一層無神經(jīng)元的組織將皮層與軟腦膜分隔開。各層至少都有一層細(xì)胞，伸出大量的稱為頂樹突的樹突，這些頂樹突會(huì)伸入到第一層，在那里形成眾多的分叉。大腦皮層的細(xì)胞結(jié)構(gòu)

分子層Molecularlayer軟腦膜Pialsurface頂樹突Apicaldentrite短吻鱷大鼠5.皮層神經(jīng)元都是呈層狀排列的，而且絕大部分神經(jīng)元胞體與腦的表面發(fā)育過程中大腦皮層的改變6.發(fā)育過程中大腦皮層的改變6.神經(jīng)細(xì)胞的增殖Neuronalproliferation神經(jīng)細(xì)胞的遷移Neuronalmigration神經(jīng)細(xì)胞分化Neuraldifferentiation軸突伸展Axonguidance突觸形成Synaptogenesis神經(jīng)細(xì)胞的死亡Neuronaldeath大腦皮層的形成7.神經(jīng)細(xì)胞的增殖Neuronalproliferation神經(jīng)細(xì)胞的增殖

NeuronalProliferation8.神經(jīng)細(xì)胞的增殖8.MG1G2S神經(jīng)細(xì)胞增殖的舞蹈表演室層邊緣層腦室側(cè)軟膜側(cè)囊泡壁250，000perminute------------------------1011neuronsOnlyafewmonths9.MG1G2S神經(jīng)細(xì)胞增殖的舞蹈表演室層邊緣層腦室側(cè)軟膜側(cè)囊泡???10.???10.內(nèi)因說外因說11.內(nèi)因說外因說11.G1期的時(shí)程決定分裂方式N,neuron;P,precursorcell.MCBA細(xì)胞命運(yùn)決定因子12.G1期的時(shí)程決定分裂方式N,neuron;MCBA細(xì)胞轉(zhuǎn)錄因子決定細(xì)胞命運(yùn)細(xì)胞命運(yùn)的決定(cell–fatedetermination)---------Notch-1和numb蛋白的不均勻分布

13.轉(zhuǎn)錄因子決定細(xì)胞命運(yùn)細(xì)胞命運(yùn)的決定(cell–fated不對稱分裂決定細(xì)胞命運(yùn)1mothercellproduces≈10,000daughtercells250，000/minute------------------------1011neuronsOnlyafewmonths?14.不對稱分裂決定細(xì)胞命運(yùn)1mothercellprodu神經(jīng)細(xì)胞的遷移和分化NeuronalMigrationandProliferation15.神經(jīng)細(xì)胞的遷移和分化15.[3H]thymidineDiI,DiO,hydrophilicdyeGFPNolabel:C.elegansBromodeoxyuridine(BrDu)細(xì)胞標(biāo)記方法16.[3H]thymidineDiI,DiO,hydroph特異性表達(dá)某種容易檢測得到的基因17.特異性表達(dá)某種容易檢測得到的基因17.J.B.Angevine,etal..Nature192:766-768,1961注射:妊娠11th,13th,15th,or17thdays檢測:注射后1hror出生后10thdayResults:Methods:Conclusion1:皮層細(xì)胞主要來源于側(cè)腦室室管膜。注射后1hr檢測:

細(xì)胞位于室管膜附近。神經(jīng)細(xì)胞遷移的證據(jù)18.J.B.Angevine,etal..NatureShownareentireanteroposteriorextentsofthecerebralcortex.15thd11thd13thd17thdNeuronsmigrate.2.Latergenerationsof postmitoticneurons migrateoutbeyond earliercellsConclusions19.ShownareentireanteroposteriInside-Out”GradientofCerebralCortexFormationintheRhesusMonkey20.Inside-Out”GradientofCerebr-

Inside-out較早分化的較大神經(jīng)元先遷移并形成最內(nèi)層，依次順序向外；而較晚分化的較小神經(jīng)元?jiǎng)t通過已形成的層次遷移并形成其外側(cè)新的層次；不論皮質(zhì)的什么區(qū)域，其最內(nèi)層總是最早分化，而最外層則最后分化。邊緣層室層放射狀膠質(zhì)細(xì)胞突起21.-Inside-out較早分化的較大神經(jīng)元先遷移r:rodcell桿狀雙核細(xì)胞t:terminalofarodcellbp:bipolarcell兩極(神經(jīng))細(xì)胞mg：glialcell神經(jīng)膠質(zhì)細(xì)胞22.22.InternalTimingMechanism內(nèi)在時(shí)間機(jī)制ThetimeorthenumberofcelldivisionPrecursorcellsDevelopmentalfate23.InternalTimingMechanismThetCommunityMechanism環(huán)境作用機(jī)制PrecursorcellsDevelopmentalfateInduciblecuesthatchangewithtime24.CommunityMechanismPrecursorc神經(jīng)元遷移的方式根據(jù)神經(jīng)元遷移的方向：放射性遷移：radialmigration

切線性遷移：tangentialmigration

25.神經(jīng)元遷移的方式根據(jù)神經(jīng)元遷移的方向：25.EM:Golgi-stainedfetalmacaquetelencephalonRadialfibersextendingfromparentcellbodiestothepialsurface,wheretheyterminateinacharacteristicendfoot.高爾基染色法－鉻酸鹽－硝酸銀染色法26.EM:Golgi-stainedfetalmacaquNeuronsmigratealongradialglialcellstotheirfinallayers(3000mm)27.Neuronsmigratealongradialgradial-directedcorticalneuronalmigration

放射狀皮層神經(jīng)細(xì)胞遷移migration:inside-firstoutside-lastBielasetal.,200428.radial-directedcorticalneuroRadialglialcelldivision放射狀神經(jīng)膠質(zhì)細(xì)胞分裂29.Radialglialcelldivision29.神經(jīng)細(xì)胞遷移和分化的認(rèn)識(shí)過程30.神經(jīng)細(xì)胞遷移和分化的認(rèn)識(shí)過程30.神經(jīng)細(xì)胞遷移的舞蹈表演31.神經(jīng)細(xì)胞遷移的舞蹈表演31.Thearrowspointtothetipoftheleadingprocess.Initialventricle-directed;Subsequentlytowardsthepialsurface.32.ThearrowspointtothetipofTwomodesofradialmigration放射性遷移的兩種方式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切線性遷移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分子層43.DefectsinneuronalmigrationBPositionofcellsbornatspecificdevelopmentaltimesisinvertedintheadultreelercerebralcortex44.PositionofcellsbornatspecdefectsinneuronalmigrationTissirandGoffinet,200345.defectsinneuronalmigrationTTheoveralldivisionsofthecerebralwallareobviousinreeler.Butthecorticalplateisdisorganizedandcellsaredisplacedbyfibersthatrunobliquelyinthecerebralwall.ManysubplatecellsarelocatedwiththeCajal-Retziuscellsinarelativelycell-denseregionknownasthesuperplate(spp).Corticalplateneurons(gray)positionsbetweentheCajal-Retziuscells(black)thatproduceReelin(stipples)andthesubplatelayer.Corticalplateneuronsfailstomigratepastthesubplateandinsteadaccumulatesinadisorganizedfashioninthesuperplate.46.Theoveralldivisionsofthec思考題1、神經(jīng)元遷移的形式2、神經(jīng)元細(xì)胞放射性遷移的兩種方式47.思考題1、神經(jīng)元遷移的形式47.神經(jīng)系統(tǒng)的發(fā)育48.神經(jīng)系統(tǒng)的發(fā)育1.本圖反應(yīng)了胚胎神經(jīng)系統(tǒng)的早期發(fā)育過程.a)最初的胚胎中樞神經(jīng)系統(tǒng)從薄層的外胚層開始發(fā)育.b)在神經(jīng)系統(tǒng)發(fā)育中重要的第一步:神經(jīng)溝的形成;c)神經(jīng)溝壁,即神經(jīng)褶向中靠攏并融合,形成神經(jīng)管;d)隨著神經(jīng)管的生長,部分外胚層內(nèi)陷到表層下,形成神經(jīng)嵴,最后發(fā)育成外周神經(jīng)系統(tǒng).神經(jīng)管神經(jīng)嵴體節(jié)神經(jīng)褶神經(jīng)溝中胚層內(nèi)胚層神經(jīng)板復(fù)習(xí)49.本圖反應(yīng)了胚胎神經(jīng)系統(tǒng)的早期發(fā)育過程.a)最初的胚胎中樞腦的分化神經(jīng)管前腦中腦后腦視泡端腦泡間腦視神經(jīng)、視網(wǎng)膜大腦皮層、白質(zhì)、嗅球丘腦、下丘腦、腦室頂蓋---上丘、下丘被蓋中腦水管小腦腦橋延髓第四腦室復(fù)習(xí)50.腦的分化神經(jīng)管前腦中腦后腦視泡端腦泡間腦視神經(jīng)、視網(wǎng)膜大腦皮大腦皮層的形態(tài)新皮層嗅皮層海馬嗅裂側(cè)腦室哺乳動(dòng)物的三種皮層新皮層Neocortex，僅存于哺乳動(dòng)物嗅皮層Olfactorycortex海馬Hippocampus嗅裂Rhinalfissure側(cè)腦室Lateralventricle舊皮層或古皮層51.大腦皮層的形態(tài)新皮層嗅皮層海馬嗅裂側(cè)腦室哺乳動(dòng)物的三種皮層新皮層神經(jīng)元都是呈層狀排列的，而且絕大部分神經(jīng)元胞體與腦的表面平行。分子層:最靠近表面的神經(jīng)細(xì)胞層,由一層無神經(jīng)元的組織將皮層與軟腦膜分隔開。各層至少都有一層細(xì)胞，伸出大量的稱為頂樹突的樹突，這些頂樹突會(huì)伸入到第一層，在那里形成眾多的分叉。大腦皮層的細(xì)胞結(jié)構(gòu)

分子層Molecularlayer軟腦膜Pialsurface頂樹突Apicaldentrite短吻鱷大鼠52.皮層神經(jīng)元都是呈層狀排列的，而且絕大部分神經(jīng)元胞體與腦的表面發(fā)育過程中大腦皮層的改變53.發(fā)育過程中大腦皮層的改變6.神經(jīng)細(xì)胞的增殖Neuronalproliferation神經(jīng)細(xì)胞的遷移Neuronalmigration神經(jīng)細(xì)胞分化Neuraldifferentiation軸突伸展Axonguidance突觸形成Synaptogenesis神經(jīng)細(xì)胞的死亡Neuronaldeath大腦皮層的形成54.神經(jīng)細(xì)胞的增殖Neuronalproliferation神經(jīng)細(xì)胞的增殖

NeuronalProliferation55.神經(jīng)細(xì)胞的增殖8.MG1G2S神經(jīng)細(xì)胞增殖的舞蹈表演室層邊緣層腦室側(cè)軟膜側(cè)囊泡壁250，000perminute------------------------1011neuronsOnlyafewmonths56.MG1G2S神經(jīng)細(xì)胞增殖的舞蹈表演室層邊緣層腦室側(cè)軟膜側(cè)囊泡???57.???10.內(nèi)因說外因說58.內(nèi)因說外因說11.G1期的時(shí)程決定分裂方式N,neuron;P,precursorcell.MCBA細(xì)胞命運(yùn)決定因子59.G1期的時(shí)程決定分裂方式N,neuron;MCBA細(xì)胞轉(zhuǎn)錄因子決定細(xì)胞命運(yùn)細(xì)胞命運(yùn)的決定(cell–fatedetermination)---------Notch-1和numb蛋白的不均勻分布

60.轉(zhuǎn)錄因子決定細(xì)胞命運(yùn)細(xì)胞命運(yùn)的決定(cell–fated不對稱分裂決定細(xì)胞命運(yùn)1mothercellproduces≈10,000daughtercells250，000/minute------------------------1011neuronsOnlyafewmonths?61.不對稱分裂決定細(xì)胞命運(yùn)1mothercellprodu神經(jīng)細(xì)胞的遷移和分化NeuronalMigrationandProliferation62.神經(jīng)細(xì)胞的遷移和分化15.[3H]thymidineDiI,DiO,hydrophilicdyeGFPNolabel:C.elegansBromodeoxyuridine(BrDu)細(xì)胞標(biāo)記方法63.[3H]thymidineDiI,DiO,hydroph特異性表達(dá)某種容易檢測得到的基因64.特異性表達(dá)某種容易檢測得到的基因17.J.B.Angevine,etal..Nature192:766-768,1961注射:妊娠11th,13th,15th,or17thdays檢測:注射后1hror出生后10thdayResults:Methods:Conclusion1:皮層細(xì)胞主要來源于側(cè)腦室室管膜。注射后1hr檢測:

細(xì)胞位于室管膜附近。神經(jīng)細(xì)胞遷移的證據(jù)65.J.B.Angevine,etal..NatureShownareentireanteroposteriorextentsofthecerebralcortex.15thd11thd13thd17thdNeuronsmigrate.2.Latergenerationsof postmitoticneurons migrateoutbeyond earliercellsConclusions66.ShownareentireanteroposteriInside-Out”GradientofCerebralCortexFormationintheRhesusMonkey67.Inside-Out”GradientofCerebr-

Inside-out較早分化的較大神經(jīng)元先遷移并形成最內(nèi)層，依次順序向外；而較晚分化的較小神經(jīng)元?jiǎng)t通過已形成的層次遷移并形成其外側(cè)新的層次；不論皮質(zhì)的什么區(qū)域，其最內(nèi)層總是最早分化，而最外層則最后分化。邊緣層室層放射狀膠質(zhì)細(xì)胞突起68.-Inside-out較早分化的較大神經(jīng)元先遷移r:rodcell桿狀雙核細(xì)胞t:terminalofarodcellbp:bipolarcell兩極(神經(jīng))細(xì)胞mg：glialcell神經(jīng)膠質(zhì)細(xì)胞69.22.InternalTimingMechanism內(nèi)在時(shí)間機(jī)制ThetimeorthenumberofcelldivisionPrecursorcellsDevelopmentalfate70.InternalTimingMechanismThetCommunityMechanism環(huán)境作用機(jī)制PrecursorcellsDevelopmentalfateInduciblecuesthatchangewithtime71.CommunityMechanismPrecursorc神經(jīng)元遷移的方式根據(jù)神經(jīng)元遷移的方向：放射性遷移：radialmigration

切線性遷移：tangentialmigration

72.神經(jīng)元遷移的方式根據(jù)神經(jīng)元遷移的方向：25.EM:Golgi-stainedfetalmacaquetelencephalonRadialfibersextendingfromparentcellbodiestothepialsurface,wheretheyterminateinacharacteristicendfoot.高爾基染色法－鉻酸鹽－硝酸銀染色法73.EM:Golgi-stainedfetalmacaquNeuronsmigratealongradialglialcellstotheirfinallayers(3000mm)74.Neuronsmigratealongradialgradial-directedcorticalneuronalmigration

放射狀皮層神經(jīng)細(xì)胞遷移migration:inside-firstoutside-lastBielasetal.,200475.radial-directedcorticalneuroRadialglialcelldivision放射狀神經(jīng)膠質(zhì)細(xì)胞分裂76.Radialglialcelldivision29.神經(jīng)細(xì)胞遷移和分化的認(rèn)識(shí)過程77.神經(jīng)細(xì)胞遷移和分化的認(rèn)識(shí)過程30.神經(jīng)細(xì)胞遷移的舞蹈表演78.神經(jīng)細(xì)胞遷移的舞蹈表演31.Thearrowspointtothetipoftheleadingprocess.Initialventricle-directed;Subsequentlytowardsthepialsurface.79.ThearrowspointtothetipofTwomodesofradialmigration放射性遷移的兩種方式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切線性遷移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