Molecular mechanism for generating and regenerating neuronal network by CNR family

CNR家族生成和再生神经网络的分子机制

基本信息

批准号：
14104025
负责人：
YAGI Takeshi
金额：
$ 72.88万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (S)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-14104025/
关键词：
cadherin neuron neural network divesity genome gene cluster gene regulation mouse 脳神経行動 Fyn CNR 脳シナプストカドヘリン心

项目摘要

Brain is a complex system which is composed of enormous number of diverse neurons. CNR/Protocadherin (Pcdh) family is constituted with gene cluster like immunoglobulin and T cell receptor genes. The CNR/Pcdh proteins are localized in synapses and developmental axons. They are differentially expressed in individual neurons. In this project, to examine molecular mechanism for neural network formation and rearrangement, we focus to the CNR/Pcdh family in the brain. This project demonstrated that 1) mouse CNR1 (Pcdha4) protein gains cell adhesion activity via active integrin proteins, 2) we firstly revealed protein structure of protocadherin family by NMR spectroscopy, 3) CNR/Pcdha proteins highly express in the developmental axons and decline from initial formation of myelin, and their down regulation is regulated by myelination, 4) producing gene converted mice of the CNR/Pcdha family reveals their essential roles for precise neural network formation, and 5) we discover novel gene regulation of the CNR/Pcdh gene clusters in individual Purkinje cells. Thus this project successfully reveals that the diverse CNR/Pcdh family molecules play roles for cell adhesion activity, establishment for neuronal diversity and neural network formation in the brain.

大脑是一个复杂的系统，由大量不同的神经元组成。 CNR/Protocadherin（PCDH）家族由免疫球蛋白和T细胞受体基因等基因簇组成。 CNR/PCDH蛋白定位在突触和发育轴突中。它们在单个神经元中差异表达。在该项目中，为了检查神经网络形成和重排的分子机制，我们专注于大脑中的CNR/PCDH家族。 This project demonstrated that 1) mouse CNR1 (Pcdha4) protein gains cell adhesion activity via active integrin proteins, 2) we firstly revealed protein structure of protocadherin family by NMR spectroscopy, 3) CNR/Pcdha proteins highly express in the developmental axons and decline from initial formation of myelin, and their down regulation is regulated by myelination, 4) producing gene converted mice of the CNR/PCDHA家族揭示了它们在精确的神经网络形成中的重要作用，5）我们发现了单个Purkinje细胞中CNR/PCDH基因簇的新基因调节。因此，该项目成功地表明，多样化的CNR/PCDH家族分子在大脑中的神经多样性和神经网络形成起着细胞粘附活性的作用。