Regional specification and cell lineages of the vertebrate forebrain

脊椎动物前脑的区域规范和细胞谱系

基本信息

批准号：
16370096
负责人：
SHIMAMURA Kenji
金额：
$ 9.98万
依托单位：
Kumamoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16370096/
关键词：
brain development pattern formation regionalization cell lineage neural stem cell forebrain telencephalon thalamus

项目摘要

The aim of this research project was to deepen our understanding of cellular and molecular processes involved in the regional specification and histogenesis of the vertebrate forebrain. In this period of support, we made some progresses on 1) nucleus formation of the thalamus, 2) early subdivision of the telencephalic primordium, 3) cell lineage analysis of the anterior neural plate, and 4) role of the adherens junction in differentiation of the neuroepithelia. We found that the directed migration of pre-specified neurons is a possible mechanism that could convert a simple two-dimensional organization of the thalamic rudiment into the three-dimensionally complicated nuclear structure. However, chick and mouse appear to utilize different strategies for this process, suggesting that behavioral change in neurons may contribute to generation of the histological diversity of thalamus among the vertebrate species. Next, we found that Wnt signaling plays a prior role for early pallial/subpallial subdivisions of the telencephalon to hedgehog signaling, thereby strictly defining the proportion of these territories. Although we tried to identify the actual Wnt ligand by using shRNA, it was not successful so far. We also pushed it forward generating Six3 Cre-ER knock-in mouse line as a tool to analyze cell lineages of different parts of the anterior neural plate over time. We found that the disruption of the adherens junction by anti-N-cadherin treatment resulted in precautious neuronal differentiation in the neural tube. Our experimental results suggest that Notch and its ligand interaction is most likely to take place in the vicinity of the junctional structure. We will continue to investigate its precise role in the maintenance of the neural progenitor cells in the context of the regionally distinct histogenesis of the forebrain.

该研究项目的目的是加深我们对脊椎动物前脑区域规范和组织发生涉及的细胞和分子过程的理解。在这一时期，我们在1）丘脑的核形成方面取得了一些进展，2）尾脑原基的早期细分，3）前神经板的细胞谱系分析，以及4）附着素连接在神经上皮分化中的作用。我们发现，预先指定的神经元的定向迁移是一种可能的机制，可以将丘脑姓的简单二维组织转化为三维复杂的核结构。但是，小鸡和小鼠似乎利用了这一过程的不同策略，这表明神经元的行为改变可能会导致脊椎动物物种中丘脑的组织学多样性的产生。接下来，我们发现WNT信号对于远程脑的早期苍白球/副局部亚分支起着刺猬信号的先验作用，从而严格地定义了这些领土的比例。尽管我们试图通过使用shRNA来识别实际的Wnt配体，但到目前为止尚未成功。我们还将其向前推动，生成了63个CRE-ER敲入小鼠系列，作为一种工具，可以随着时间的推移分析前神经板的不同部位的细胞谱系。我们发现，通过抗N-钙粘蛋白治疗对粘附连接的破坏导致神经管中的神经元分化。我们的实验结果表明，Notch及其配体相互作用最有可能发生在连接结构的附近。我们将继续研究其在前脑区域不同的组织发生的背景下，在维持神经祖细胞中的精确作用。