神经元的迁移课件

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,1,神经系统的发育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,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,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,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,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,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,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,发育过程中大脑皮层的改变,6,发育过程中大脑皮层的改变6,神经细胞的增殖,Neuronal proliferation,神经细胞的迁移,Neuronal migration,神经细胞分化,Neural differentiation,轴突伸展,Axon guidance,突触形成,Synaptogenesis,神经细胞的死亡,Neuronal death,大脑皮层的形成,7,神经细胞的增殖 Neuronal proliferation,神经细胞的增殖,Neuronal Proliferation,8,神经细胞的增殖8,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,MG1G2S神经细胞增殖的舞蹈表演室层边缘层脑室侧软膜侧囊泡,?,?,?,10,?10,内因说,外因说,11,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,G1 期的时程决定分裂方式N,neuron;MCBA细胞,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,转录因子决定细胞命运细胞命运的决定(cell fate d,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,不对称分裂决定细胞命运1 mother cell produ,神经细胞的迁移和分化,Neuronal Migration and Proliferation,15,神经细胞的迁移和分化15,3Hthymidine,DiI,DiO,hydrophilic dye,GFP,No label:C.elegans,Bromodeoxyuridine(BrDu),细胞标记方法,16,3HthymidineDiI,DiO,hydroph,特异性表达某种容易检测得到的基因,17,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,J.B.Angevine,et al.Nature,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,Shown are entire anteroposteri,Inside-Out,”,Gradient of Cerebral Cortex Formation in the Rhesus Monkey,20,Inside-Out”Gradient of Cerebr,-,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,-Inside-out较早分化的较大神经元先迁移,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,22,22,Internal Timing Mechanism,内在时间机制,The time or the number of cell division,Precursor cells,Developmental fate,23,Internal Timing MechanismThe t,Community Mechanism,环境作用机制,Precursor cells,Developmental fate,Inducible cues,that change with time,24,Community MechanismPrecursor c,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,神经元迁移的方式根据神经元迁移的方向：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,EM:Golgi-stained fetal macaqu,Neurons migrate along radial glial cells,to their final layers(3000,m,m),27,Neurons migrate along radial g,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-directed cortical neuro,Radial glial cell division,放射状神经胶质细胞分裂,29,Radial glial cell division29,神经细胞迁移和分化的认识过程,30,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,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,The arrows point to the tip of,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,Two modes of radial migrationL,A cell displaying somal translocation in an E14 cortical slice,Nadarajah et al.,2001,34,A cell displaying somal transl,Translocating cells with branched,pial-directed processes,Nadarajah et al.,2001,35,Translocating cells with branc,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,Bielas,Annu.Rev.Cell Dev.B,Non-ratial/tangential migration,切线性迁移,38,Non-ratial/tangential migratio,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,Major routes of