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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

基板是新皮层中最早发育的一层。层中的神经元（SP神经元）被认为对皮质板中的神经元起先锋作用，皮质板中的神经元发育较晚。为了阐明这些作用，我计划制造缺乏SP神经元的模型小鼠。早期近端启动子（early proximal promoter，EPP）是髓鞘碱性蛋白基因中golli启动子的一部分，在SP神经元中可持续表达。已知反向半胱天冬酶-3会引起表达它的细胞立即死亡，我计划通过在EPP的控制下递送反向半胱天冬酶-3来删除亚板。然而，人们发现，即使SP神经元数量减少，也会导致小鼠大脑的广泛缺陷和过早死亡，使发育分析变得困难。然后，我试图干扰SP神经元的放射状神经突所发挥的特定功能。组成型活性钙调神经磷酸酶，通过缺失钙-Ca ...更多信息发现天然钙调磷酸酶的I调节域抑制神经突的延伸。我试图分析在EPP控制下表达组成型活性钙调神经磷酸酶的小鼠中SP神经元的变化及其影响。为了与SP神经元受到干扰的小鼠进行比较，我分析了表达过量白细胞介素-9的转基因小鼠的新皮层发育，其中，我发现，SP神经元的发育增强。一项关于识别任务的研究是通过训练转基因小鼠触摸面板而不是推动杠杆来响应光刺激来实现的。结果表明，转基因小鼠的学习成绩明显低于相同遗传背景的对照小鼠。强烈的免疫反应被发现附着在迁移的神经元在基板，中间带和脑室下区的小胶质细胞。这表明小胶质细胞参与了神经元的迁移或神经突的延伸。少