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A study on the development of the cerebral neocortex using mice with perturbations on the subplate neurons

利用小鼠亚板神经元扰动研究大脑新皮质的发育

基本信息

批准号：
12680781
负责人：
ISHII Kayoko
金额：
$ 2.05万
依托单位：
Keio University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12680781/
关键词：
the cerebral neocortex subplate neurones mouse embryos laminar formation golli promoter interleukin-9 層構築 golli プロモーター

项目摘要

The subplate is a layer that develops earliest in the neocortex. Neurones in the layer (SP neurones) are considered to play pioneering roles for neurones in the cortical plates, which develop later. In order to elucidated these roles, I planed to produce model mice devoid of SP neurones. The early proximal promoter (EPP), a part of golli promoter contained in myelin basic protein gene, was found to drive a strong and sustained expression of proteins in SP neurones. Reverse caspase-3 was known to elicit an immediate death in the cells that express it. I planed to delete the subplate by delivering reverse caspase-3 under the control of EPP. It was found, however, that even diminution of number of SP neurones caused extensive defects of the brain and premature death of mice to make developmental analyzes difficult. I then tried to perturb specific functions of SP neurones played by their radial neurites. Constitutively active calcineurin, which is constructed by deletion of the calcium-ca … More lmodulin regulatory domain of the native calcineurin, was found to suppress extension of neurites. I am trying to analyze changes of SP neurones and their effects in the mice that express constitutively active calcineurin under the control of EPP.In order to compare with the mice whose SP neurones are perturbed, I analyzed neocortical development of transgenic mice expressing excess interleukin-9, in which, I have found, the development of SP neurones is enhanced. A study of discrimination tasks was achieved with the transgenic mice by training them to touch a panel instead of to push lever in response to a light stimulus. The transgenic mice showed a lower achievement level than control mice with the same genetic background.A novel monoclonal antibody 4E1, which we have produced, was found to have a specific immunoreactivity in amoeboid microglia. Strong immunoreactivity was found on microglia attached to migrating neurones in the subplate, intermediate zone and subventricular zone. This suggests that microglia participates in neuronal migration or extension of neurites. Less

亚板是新皮质中发育最早的一层。这一层中的神经元(SP神经元)被认为是皮质板区神经元的先驱，皮质板区神经元发育较晚。为了阐明这些作用，我计划制造没有SP神经元的模型鼠。早期近端启动子(EPP)是髓鞘碱性蛋白基因中Golli启动子的一部分，可驱动SP神经元中蛋白质的持续表达。已知反向caspase-3会导致表达它的细胞立即死亡。我计划在EPP的控制下通过递送反向caspase-3来删除亚板。然而，研究发现，即使SP神经元的数量减少，也会导致小鼠广泛的脑缺陷和过早死亡，从而使发育分析变得困难。然后，我试图干扰由其放射状突起所发挥的SP神经元的特定功能。钙调神经磷酸酶，通过缺失钙-钙…构建更多的天然钙调神经磷酸酶的lmodin调节域，被发现可以抑制神经突起的延伸。我试图分析在EPP的控制下，表达结构性活性钙调神经磷酸酶的小鼠的SP神经元的变化及其作用。为了与受干扰的小鼠相比，我分析了过量表达IL-9的转基因小鼠的新皮质发育，我发现其中SP神经元的发育被促进。通过训练转基因小鼠触摸面板而不是推动杠杆对光刺激做出反应，对转基因小鼠的辨别任务进行了研究。转基因小鼠的成绩低于相同遗传背景的对照小鼠。我们制备的一种新的单抗4E1在阿米巴样小胶质细胞中具有特异性免疫反应。小胶质细胞附着于移行神经元的亚板、中间区和脑室下区，呈强阳性反应。这表明小胶质细胞参与了神经元的迁移或突起的延伸。较少