神經(jīng)元的分化

1、1神經(jīng)系統(tǒng)的發(fā)育孫麗榮南方醫(yī)科大學(xué)南方醫(yī)科大學(xué) 基礎(chǔ)醫(yī)學(xué)院基礎(chǔ)醫(yī)學(xué)院 神經(jīng)生物學(xué)教研室神經(jīng)生物學(xué)教研室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)3腦的分化腦的分化神神經(jīng)經(jīng)管管前腦前腦中腦中腦后腦后腦視泡視泡端腦泡端腦泡間腦間腦視神經(jīng)、視網(wǎng)膜視神經(jīng)、視網(wǎng)膜大腦皮層、白質(zhì)、嗅球大腦皮層、白質(zhì)、嗅球丘腦、下丘腦、腦室丘腦、

2、下丘腦、腦室頂蓋頂蓋-上丘、下丘上丘、下丘被蓋被蓋中腦水管中腦水管小腦小腦腦橋腦橋延髓延髓第四腦室第四腦室復(fù)習(xí)4大腦皮層的形態(tài)新皮層新皮層嗅皮層嗅皮層海馬海馬嗅裂嗅裂側(cè)腦室側(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Olfactory cortex海馬Hippocampus嗅裂Rhinal fissure側(cè)腦室Lateral ventricle舊皮層或古皮層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

3、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Molecular layer軟腦膜Pial surface頂樹突Apical dentrite短吻鱷大鼠6發(fā)育過程中大腦皮層的改變71.神經(jīng)細(xì)胞的增殖神經(jīng)細(xì)胞的增殖 Neuronal proliferation2.神經(jīng)細(xì)胞的遷移神經(jīng)細(xì)胞的遷移 Neuronal migration3.神經(jīng)細(xì)胞分化神經(jīng)細(xì)胞分化 Neural differentiation4.軸突伸展軸突伸展 Axon guidance5.突觸形成突觸形成 Synaptogenesis6.神經(jīng)細(xì)胞的死亡神經(jīng)細(xì)胞的死亡 Neuronal death大腦皮層的形成8神經(jīng)細(xì)胞的

4、增殖神經(jīng)細(xì)胞的增殖 Neuronal Proliferation9MG1G2S神經(jīng)細(xì)胞增殖的舞蹈表演神經(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250，000 per minute - 1011 neuronsOnly a few months10?11內(nèi)因說內(nèi)因說外因說外因說12G1 期的時(shí)程決定分裂方式期的時(shí)程決定分裂方式N, neuron; P, precursor cell.MCBA細(xì)胞命運(yùn)決定因子細(xì)胞命運(yùn)決定因子13轉(zhuǎn)錄因子決定細(xì)胞命運(yùn)細(xì)胞命運(yùn)的決定(cell fate determination) -Notch-1和numb蛋白的不均勻分布14不對(duì)稱分裂決定細(xì)胞命運(yùn)不對(duì)稱分裂

5、決定細(xì)胞命運(yùn)1 mother cell produces 10,000 daughter cells250，000/minute - 1011 neuronsOnly a few months?15神經(jīng)細(xì)胞的遷移和分化神經(jīng)細(xì)胞的遷移和分化Neuronal Migration and Proliferation163HthymidineDiI, DiO, hydrophilic dyeGFPNo label: C. elegansBromodeoxyuridine (BrDu) 細(xì)胞標(biāo)記方法17特異性表達(dá)某種容易檢測得到的基因18J.B. Angevine, et al. Nature 192:

6、766-768, 1961 注射注射: 妊娠妊娠11th, 13th, 15th, or 17th days 檢測檢測: 注射后注射后1 hr or 出生后出生后10th dayResults: Methods:Conclusion 1:皮層細(xì)胞主要來源于側(cè)腦室室管膜。皮層細(xì)胞主要來源于側(cè)腦室室管膜。注射后注射后1 hr檢測檢測: 細(xì)胞位于室管膜附近。細(xì)胞位于室管膜附近。神經(jīng)細(xì)胞遷移的證據(jù)19Shown are entire anteroposterior extents of the cerebral cortex.15th d11th d13th d17th d1. Neurons mig

7、rate.2. Later generations of postmitotic neurons migrate out beyond earlier cellsConclusions20Inside-Out” Gradient of Cerebral Cortex Formation in the Rhesus Monkey21 - 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；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

8、論皮質(zhì)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。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。邊緣層邊緣層室層室層放射狀膠質(zhì)細(xì)胞放射狀膠質(zhì)細(xì)胞突起突起22r: rod cell 桿狀雙核細(xì)胞t: terminal of a rod cellbp: bipolar cell兩極(神經(jīng))細(xì)胞mg： glial cell神經(jīng)膠質(zhì)細(xì)胞23Internal Timing Mechanism內(nèi)在時(shí)間機(jī)制The time or the number of cell division Precursor cellsDevelopmental fate 24Community Mec

9、hanism環(huán)境作用機(jī)制Precursor cellsDevelopmental fate Inducible cues that change with time25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： radial migration 切線性遷移： tangential migration 26EM: Golgi-stained fetal macaque telencephalonRadial fibers extending from parent cell bodies to the pial surface,where they terminate in a char

10、acteristic endfoot.高爾基染色法高爾基染色法鉻酸鹽硝酸銀染色法27Neurons migrate along radial glial cells to their final layers (3000 m mm)28radial-directed cortical neuronal migration放射狀皮層神經(jīng)細(xì)胞遷移migration:inside-firstoutside-lastBielas et al., 200429Radial glial cell division放射狀神經(jīng)膠質(zhì)細(xì)胞分裂放射狀神經(jīng)膠質(zhì)細(xì)胞分裂30神經(jīng)細(xì)胞遷移和分化的認(rèn)識(shí)過程31神經(jīng)細(xì)胞遷移的

11、舞蹈表演32The arrows point to the tip of the leading process.Initial ventricle-directed;Subsequently towards the pial surface.33Two modes of radial migration放射性遷移的兩種方式LocomotionMovement of the entire cell, including its leadingand trailing process, over considerable distancee.g., glial-guided radial mov

12、ement of neuronsTranslocationThe cell extends a leading process in the direction of migration, then moves the nucleus throughthe elongated process to its destination34A cell displaying somal translocation in an E14 cortical sliceNadarajah et al., 200135Translocating cells with branched, pial-directe

13、d processesNadarajah et al., 200136 a cell displaying presumptive glial-guided locomotion37Bielas, Annu. Rev. Cell Dev. Biol. 2004. 20:593618The two distinct forms of cortical neuron movement38Non-ratial/tangential migration切線性遷移切線性遷移39Major routes of tangential migration(1) MGE to the dorsal telenc

14、ephalon (2) CGE to dorsal telencephalon (3) Cortical-striatal boundary to the ventrolateral telencephalon (lateral cortical stream) (4) LGE to the olfactory bulb (rostral migratory stream).CGE, caudal ganglionic eminenceCTX, neocortexLGE, lateral ganglionic eminenceMGE, medial ganglionic eminenceOB,

15、 olfactory bulb40known and hypothesized routes of tangential cell migration(1) MGE to neocortex and hippocampus (2) MGE to LGE (3) corticalstriatal boundary to ventrolateral telencephalon (lateral cortical stream) (4) LGE to neocortex and hippocampus (5) CGE to dorsal telencephalon (6) LGE to olfact

16、ory bulb (rostral migratory stream) (7) Retrobulbar region to marginal zone41neurons from the medial ganglionic eminence (MGE) of the ventral telencephalon migrate toward the dorsal telencephalon. Initially, migration in the cortex is tangential but then becomes radial or oblique as neurons enter th

17、e cortical plate. 42Cell-cell interactionCell-ECM interaction43Defects in neuronal migrationBielas et al., 2004分子層44Position of cells born at specific developmental times is inverted in the adult reeler cerebral cortex45defects in neuronal migrationTissir and Goffinet, 200346The overall divisions of the cerebral wall are obvious in reeler. But the cortical plate is disorganized and cells are displaced by fibers that run obliquely in the cerebral wall. Many subplate cells are located with the Cajal-Retzius cells in a relatively cell-dense region known as the superplate (spp).Cortical pla