神經(jīng)系統(tǒng)的發(fā)育1a本圖反響了胚胎神經(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,局部外胚層內(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)2a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)3a大腦皮層的形態(tài)新皮層嗅皮層海馬嗅裂側(cè)腦室哺乳動物的三種皮層新皮層Neocortex，僅存于哺乳動物嗅皮層Olfactorycortex海馬Hippocampus嗅裂Rhinalfissure側(cè)腦室Lateralventricle舊皮層或古皮層4a皮層神經(jīng)元都是呈層狀排列的，而且絕大局部神經(jīng)元胞體與腦的外表平行。分子層:最靠近外表的神經(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5a發(fā)育過程中大腦皮層的改變6a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7a神經(jīng)細(xì)胞的增殖

NeuronalProliferation8aMG1G2S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------------------------1011neuronsOnlyafewmonths9a???10a內(nèi)因說外因說11aG1期的時程決定分裂方式N,neuron;P,precursorcell.MCBA細(xì)胞命運(yùn)決定因子12a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

13a不對稱分裂決定細(xì)胞命運(yùn)1mothercellproduces≈10,000daughtercells250，000/minute------------------------1011neuronsOnlyafewmonths?14a神經(jīng)細(xì)胞的遷移和分化NeuronalMigrationandProliferation15a[3H]thymidineDiI,DiO,hydrophilicdyeGFPNolabel:C.elegansBromodeoxyuridine(BrDu)細(xì)胞標(biāo)記方法16a特異性表達(dá)某種容易檢測得到的基因17aJ.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)18aShownareentireanteroposteriorextentsofthecerebralcortex.15thd11thd13thd17thdNeuronsmigrate.2.Latergenerationsof postmitoticneurons migrateoutbeyond earliercellsConclusions19aInside-Out〞GradientofCerebralCortexFormationintheRhesusMonkey20a-

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)元那么通過已形成的層次遷移并形成其外側(cè)新的層次；不管皮質(zhì)的什么區(qū)域，其最內(nèi)層總是最早分化，而最外層那么最后分化。邊緣層室層放射狀膠質(zhì)細(xì)胞突起21ar: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22aInternalTimingMechanism內(nèi)在時間機(jī)制ThetimeorthenumberofcelldivisionPrecursorcellsDevelopmentalfate23aCommunityMechanism環(huán)境作用機(jī)制PrecursorcellsDevelopmentalfateInduciblecuesthatchangewithtime24a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

25aEM:Golgi-stainedfetalmacaquetelencephalonRadialfibersextendingfromparentcellbodiestothepialsurface,wheretheyterminateinacharacteristicendfoot.高爾基染色法－鉻酸鹽－硝酸銀染色法26aNeuronsmigratealongradialglialcellstotheirfinallayers(3000mm)27aradial-directedcorticalneuronalmigration

放射狀皮層神經(jīng)細(xì)胞遷移migration:inside-firstoutside-lastBielasetal.,200428aRadialglialcelldivision放射狀神經(jīng)膠質(zhì)細(xì)胞分裂29a神經(jīng)細(xì)胞遷移和分化的認(rèn)識過程30a神經(jīng)細(xì)胞遷移的舞蹈表演31aThearrowspointtothetipoftheleadingprocess.Initialventricle-directed;Subsequentlytowardsthepialsurface.32aTwomodesofradialmigration放射性遷移的兩種方式LocomotionMovementoftheentirecell,includingitsleadingandtrailingprocess,overconsiderabledistancee.g.,glial-guidedradialmovementofneuronsTranslocationThecellextendsaleadingprocessinthedirectionofmigration,thenmovesthenucleusthroughtheelongatedprocesstoitsdestination33aAcelldisplayingsomaltranslocationinanE14corticalsliceNadarajahetal.,200134aTranslocatingcellswithbranched,pial-directedprocessesNadarajahetal.,200135a

acelldisplayingpresumptiveglial-guidedlocomotion36aBielas,Annu.Rev.CellDev.Biol.2004.20:593–618Thetwodistinctformsofcorticalneuronmovement37aNon-ratial/tangentialmigration切線性遷移38aMajorroutesoftangentialmigration(1)MGEtothedorsaltelencephalon(2)CGEtodorsaltelencephalon(3)Cortical-striatalboundarytotheventrolateraltelencephalon(lateralcorticalstream)(4)LGEtotheolfactorybulb(rostralmigratorystream).CGE,caudalganglioniceminenceCTX,neocortexLGE,lateralganglioniceminenceMGE,medialganglioniceminenceOB,olfactorybulb39aknownandhypothesizedroutesoftangentialcellmigration(1)MGEtoneocortexandhippocampus(2)MGEtoLGE(3)cortical–striatalboundaryto ventrolateraltelencephalon (lateralcorticalstream)(4)LGEtoneocortexandhippocampus(5)CGEtodorsaltelencephalon(6)LGEtoolfactorybulb (rostralmigratorystream)(7)Retrobulbarregiontomarginalzone40aneuronsfromthemedialganglioniceminence(MGE)oftheventraltelencephalonmigratetowardthedorsaltelencephalon.Initially,migrationinthecortexistangentialbutthenbecomesradialorobliqueasneuronsenterthecorticalplate.41aCell-cellinteractionCell-ECMinteraction42aDefectsinneuronalmigrationBielasetal.,2004分子層43aPositionofcellsbornatspecificdevelopmentaltimesisinvertedintheadultreelercerebralcortex44adefectsinneuronalmigrationTissirandGoffinet,200345aTheoveralldivisionsofthecerebralwallareobviousinreeler.Butthecorticalplateisdisorganizedandcellsaredisplacedbyfibersthatrunobliquelyinthecerebralwall.ManysubplatecellsarelocatedwiththeCajal-Retziuscellsinarelativelycell-denseregionknownasthesuperplate(spp).Corticalplateneu