神經(jīng)元的分化課件

神經(jīng)系統(tǒng)的發(fā)育1本圖反應了胚胎神經(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)板復習2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習3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。

大腦皮層的細胞結(jié)構(gòu)

分子層Molecularlayer軟腦膜Pialsurface頂樹突Apicaldentrite短吻鱷大鼠5發(fā)育過程中大腦皮層的改變6神經(jīng)細胞的增殖Neuronalproliferation神經(jīng)細胞的遷移Neuronalmigration神經(jīng)細胞分化Neuraldifferentiation軸突伸展Axonguidance突觸形成Synaptogenesis神經(jīng)細胞的死亡Neuronaldeath大腦皮層的形成7神經(jīng)細胞的增殖

NeuronalProliferation8???10G1期的時程決定分裂方式N,neuron;P,precursorcell.MCBA細胞命運決定因子12不對稱分裂決定細胞命運1mothercellproduces≈10,000daughtercells250，000/minute------------------------1011neuronsOnlyafewmonths?14神經(jīng)細胞的遷移和分化NeuronalMigrationandProliferation15[3H]thymidineDiI,DiO,hydrophilicdyeGFPNolabel:C.elegansBromodeoxyuridine(BrDu)細胞標記方法16特異性表達某種容易檢測得到的基因17J.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:皮層細胞主要來源于側(cè)腦室室管膜。注射后1hr檢測:細胞位于室管膜附近。神經(jīng)細胞遷移的證據(jù)18Inside-Out”GradientofCerebralCortexFormationintheRhesusMonkey20-

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)元則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)細胞突起21InternalTimingMechanism內(nèi)在時間機制ThetimeorthenumberofcelldivisionPrecursorcellsDevelopmentalfate23CommunityMechanism環(huán)境作用機制PrecursorcellsDevelopmentalfateInduciblecuesthatchangewithtime24EM:Golgi-stainedfetalmacaquetelencephalonRadialfibersextendingfromparentcellbodiestothepialsurface,wheretheyterminateinacharacteristicendfoot.高爾基染色法－鉻酸鹽－硝酸銀染色法26Neuronsmigratealongradialglialcellstotheirfinallayers(3000mm)27radial-directedcorticalneuronalmigration

放射狀皮層神經(jīng)細胞遷移migration:inside-firstoutside-lastBielasetal.,200428神經(jīng)細胞遷移和分化的認識過程30神經(jīng)細胞遷移的舞蹈表演31Thearrowspointtothetipoftheleadingprocess.Initialventricle-directed;Subsequentlytowardsthepialsurface.32Twomodesofradialmigration放射性遷移的兩種方式LocomotionMovementoftheentirecell,includingitsleadingandtrailingprocess,overconsiderabledistancee.g.,glial-guidedradialmovementofneuronsTranslocationThecellextendsaleadingprocessinthedirectionofmigration,thenmovesthenucleusthroughtheelongatedprocesstoitsdestination33AcelldisplayingsomaltranslocationinanE14corticalsliceNadarajahetal.,200134Translocatingcellswithbranched,pial-directedprocessesNadarajahetal.,200135

acelldisplayingpresumptiveglial-guidedlocomotion36Bielas,Annu.Rev.CellDev.Biol.2004.20:593–618Thetwodistinctformsofcorticalneuronmovement37Non-ratial/tangentialmigration切線性遷移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分子層43Positionofcellsbornatspecificdevelopmentaltimesisinvertedintheadultreelercerebralcortex44defectsinneuronalmigrationTissirandGoffinet,200345Theoveralldivisionsofthecerebralwallareobviousinreeler.Butthecorticalplateisdisorganizedandcellsaredisplacedbyfibersthatrunobliquelyinthecerebralwall.ManysubplatecellsarelocatedwiththeCajal-Retziuscellsinarelativelycell-denseregionknownasthesuperplate(spp).Corticalplateneurons(gray)positionsbetweentheCajal