神经元的分化.ppt

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,神经系统的发育,孙丽荣,南方医科大学 基础医学院 神经生物学教研室,1,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,2,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,3,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,Olfactory cortex,海马,Hippocampus,嗅裂Rhinal fissure,侧脑室Lateral ventricle,旧皮层或古皮层,4,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Molecular layer,软脑膜Pial surface,顶树突Apical dentrite,短吻鳄,大鼠,5,发育过程中大脑皮层的改变,6,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,250，000 per minute,-,10,11,neurons,Only a few months,9,?,?,?,10,内因说,外因说,11,G1 期的时程决定分裂方式,N,neuron;,P,precursor cell.,MC,B,A,细胞命运决定因子,12,转录因子决定细胞命运,细胞命运的决定(cell fate determination),-,Notch-1,和numb蛋白的不均匀分布,13,不对称分裂决定细胞命运,1 mother cell produces 10,000 daughter cells,250，000/minute -10,11,neurons,Only a few months,?,14,神经细胞的迁移和分化,Neuronal Migration and Proliferation,15,3Hthymidine,DiI,DiO,hydrophilic dye,GFP,No label:C.elegans,Bromodeoxyuridine(BrDu),细胞标记方法,16,特异性表达某种容易检测得到的基因,17,J.B.Angevine,et al.Nature 192:766-768,1961,注射:妊娠11,th,13,th,15,th,or 17,th,days,检测:注射后1 hr,or 出生后10,th,day,Results:,Methods:,Conclusion 1:皮层细胞主要来源于侧脑室室管膜。,注射后1 hr检测:,细胞位于室管膜附近。,神经细胞迁移的证据,18,Shown are entire anteroposterior extents,of the cerebral cortex.,15th d,11th d,13th d,17th d,Neurons migrate.,2.Later generations of,postmitotic,neurons,migrate out beyond,earlier cells,Conclusions,19,Inside-Out”Gradient of Cerebral Cortex Formation in the Rhesus Monkey,20,-,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,21,r:rod cell 杆状双核细胞,t:terminal of a rod cell,bp:bipolar cell,两极(神经)细胞,mg：glial cell,神经胶质细胞,22,Internal Timing Mechanism,内在时间机制,The time or the number of cell division,Precursor cells,Developmental fate,23,Community Mechanism,环境作用机制,Precursor cells,Developmental fate,Inducible cues,that change with time,24,神经元迁移的方式,根据神经元迁移的方向：,放射性迁移：,radial migration,切线性迁移：,tangential migration,25,EM:,Golgi-stained f,etal macaque,telencephalon,Radial fibers extending from,parent cell bodies to the pial surface,where they terminate in a,characteristic endfoot.,高尔基染色法,铬酸盐硝酸银染色法,26,Neurons migrate along radial glial cells,to their final layers(3000,m,m),27,radial-directed cortical neuronal migration,放射状皮层神经细胞迁移,migration:,inside-first,outside-last,Bielas et al.,2004,28,Radial glial cell division,放射状神经胶质细胞分裂,29,神经细胞迁移和分化的认识过程,30,神经细胞迁移的舞蹈表演,31,The arrows point to the tip of,the leading process.,Initial ventricle-directed;,Subsequently towards,the pial surface.,32,Two modes of radial migration,放射性迁移的两种方式,Locomotion,Movement of the entire cell,including its leading,and trailing process,over considerable distance,e.g.,glial-guided radial movement of neurons,Translocation,The cell extends a leading process in the direction,of migration,then moves the nucleus through,the elongated process to its destination,33,A cell displaying somal translocation in an E14 cortical slice,Nadarajah et al.,2001,34,Translocating cells with branched,pial-directed processes,Nadarajah et al.,2001,35,a cell displaying presumptive glial-guided locomotion,36,Bielas,Annu.Rev.Cell Dev.Biol.2004.20:593618,The two distinct forms of cortical neuron movement,37,Non-ratial/tangential migration,切线性迁移,38,Major routes of tangential migration,(1)MGE to the dorsal telencephalon,(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 eminence,CTX,neocortex,LGE,lateral ganglionic eminence,MGE,medial ganglionic eminence,OB,olfactory bulb,39,known 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 olfactory bulb,(rostral migratory stream),(7)Retrobulbar region to marginal zone,40,neurons 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 the cortical plate.,41,Cell-cell interaction,Cell-ECM interaction42,Defects in neuronal migration,Bielas et al.,2004,分子层,43,Position of cells born at specific developmental times,is inverted in the adult,reeler,cerebral cortex,44,defects in neuronal migration,Tissir and Goffinet,2003,45,The 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 plate neurons(gray)positions,between the Cajal-Retzius cells(black),that produce Reelin(,stipples,)and the,subplate layer.,Cortical plate neurons fails to migrate,past the subplate and instead accumulates,in a disorganized fashion in the superplate.,46,思考题,1、神经元迁移的形式,2、神经元细胞放射性迁移的两种方式,47,