神经元的分化

44
defects in neuronal migration
45 Tissir and Goffinet, 2003
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).
15
[3H]thymidine Bromodeoxyuridine (BrDu) DiI, DiO, hydrophilic dye GFP No label: C. elegans
细胞标记方法
16
特异性表达某种容易 检测得到的基因
17
神经细胞迁移的证据
Methods:
J.B. Angevine, et al.. Nature 192:766-768, 1961
20
-
Inside-out
边缘层
突起 放射状胶质细胞 室层
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。 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
外因说
11
G1 期的时程决定分裂方式
B MC A
细胞命运决定因子
N, neuron; P, precursor cell.
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
41
Cell-cell interaction
Cell-ECM interaction
42
Defects in neuronal migration
分子层
43 Bielas et al., 2004
Position of cells born at specific developmental times is inverted in the adult reeler cerebral cortex
旧皮层或古皮层
4
大脑皮层的细胞结构
短吻鳄 大鼠
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，
分子层Molecular layer 软脑膜Pial surface 顶树突Apical dentrite
Developmental fate
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 fetal macaque telencephalon
Radial fibers extending from parent cell bodies to the pial surface, where they terminate in a characteristic endfoot.
(4) LGE to the olfactory bulb (rostral migratory stream).
39
known and hypothesized routes of tangential cell migration
(1) MGE to neocortex and hippocampus (2) MGE to LGE (3) cortical–striatal boundary to ventrolateral telencephalon
11th d
Conclusions 1. Neurons migrate. 2. Later generations of postmitotic neurons migrate out beyond earlier cells
13th d
15th d
17th d
19
Inside-Out” Gradient of Cerebral Cortex Formation in the Rhesus Monkey
Locomotion
Movement of the entire cell, including its leading and trailing process, over considerable distance
e.g., glial-guided radial movement of neurons
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 mm)
27
radial-directed cortical neuronal migration
放射状皮层神经细胞迁移
(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
复习
脑的分化
前脑
神 经 管
端脑泡 视泡 间脑
中脑
后脑
大脑皮层、白质、嗅球 视神经、视网膜 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 3 第四脑室
大脑皮层的形态
新皮层
侧脑室
海马
新皮层Neocortex，仅存于哺乳动物
嗅裂 嗅皮层
哺乳动物的三种皮层
嗅皮层Olfactory cortex 海马Hippocampus 嗅裂Rhinal fissure 侧脑室Lateral ventricle
?
1 mother cell produces ≈ 10,000 daughter cells 250，000/minute ------------------------ 1011 neurons Only a few months
14
神经细胞的迁移和分化
Neuronal Migration and Proliferation
这些顶树突会伸入到第一层， 在那里形成众多的分叉。
5
发育过程中大脑皮层的改变
6
大脑皮层的形成
1. 2. 3. 4. 5. 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
22
Internal Timing Mechanism
内在时间机制
Precursor cells
The time or the number of cell division
Developmental fate
23
Community Mechanism
环境作用机制
Precursor cells
Inducible cues that change with time
33
A cell displaying somal translocation in an E14 cortical slice
34
Nadarajah et al., 2001
Translocating cells with branched, pial-directed processes
35
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.
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
复习
中胚层
神经沟
神经板
神经褶
体节 神经嵴
神经管
内胚层
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. 2
(1) MGE to the dorsal telencephalon (2) CGE to dorsal telencephalon
(3) Cortical-striatal boundary to the ventrolateral telencephalon (lateral cortical stream)
7
神经细胞的增殖
Neuronal Proliferation
8
G1 软膜侧 S
边缘层
G2
囊泡壁
M
室层 脑室侧
神经细胞增殖的舞蹈表演
250，000 per minute ------------------------ 1011 neurons 9 Only a few months
?
?
?
10
内因说
Nadarajah et al., 2001
a cell displaying presumptive glial-guided locomotion
36
The two distinct forms of cortical neuron movement
Bielas, Annu. Rev. Cell Dev. Biol. 2004. 20:593–618 37
Non-ratial/tangential migration
切线性迁移
38
Major routes of tangential migration
CGE, caudal ganglionic eminence CTX, neocortex LGE, lateral ganglionic eminence MGE, medial ganglionic eminence OB, olfactory bulb
Results:
wenku.baidu.com
注射: 妊娠11th, 13th, 15th, or 17th days 检测: 注射后1 hr or 出生后10th day
注射后1 hr检测: 细胞位于室管膜附近。
Conclusion 1:皮层细胞主要来源于侧脑室室管膜。
18
Shown are entire anteroposterior extents of the cerebral cortex.
Initial ventricle-directed; Subsequently towards the pial surface.
32
Two modes of radial migration
放射性迁移的两种方式
Translocation The cell extends a leading process in the direction of migration, then moves the nucleus through the elongated process to its destination
Bielas et al., 2004
migration: inside-first outside-last
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.