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参与小脑皮层回路发育的基因的系统化和克隆。

Systematizing and cloning of genes involved in the cerebellar cortex circuit development.

机构信息

Laboratory for Molecular Neurogenesis, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, 351-0198, Saitama, Japan.

出版信息

Neurochem Res. 2011 Jul;36(7):1241-52. doi: 10.1007/s11064-011-0398-1. Epub 2011 Jan 18.

Abstract

The cerebellar cortical circuit of mammals develops via a series of magnificent cellular events in the postnatal stage of development to accomplish the formation of functional circuit architectures. The contribution of genetic factors is thought to be crucial to cerebellar development. Therefore, it is essential to analyze the underlying transcriptome during development to understand the genetic blueprint of the cerebellar cortical circuit. In this review, we introduce the profiling of large numbers of spatiotemporal gene expression data obtained by developmental time-series microarray analyses and in situ hybridization cellular mRNA mapping, and the creation of a neuroinformatics database called the Cerebellar Development Transcriptome Database. Using this database, we have identified thousands of genes that are classified into various functional categories and are expressed coincidently with related cellular developmental stages. We have also suggested the molecular mechanisms of cerebellar development by functional characterization of several identified genes (Cupidin, p130Cas, very-KIND, CAPS2) responsible for distinct cellular events of developing cerebellar granule cells. Taken together, the gene expression profiling during the cerebellar development demonstrates that the development of cerebellar cortical circuit is attributed to the complex but orchestrated transcriptome.

摘要

哺乳动物小脑皮质回路通过在出生后的发育阶段发生一系列壮观的细胞事件来发育,以完成功能性回路结构的形成。遗传因素的贡献被认为对小脑发育至关重要。因此,分析发育过程中的潜在转录组对于理解小脑皮质回路的遗传蓝图至关重要。在这篇综述中,我们介绍了通过发育时间序列微阵列分析和原位杂交细胞 mRNA 图谱获得的大量时空基因表达数据的分析,并创建了一个名为小脑发育转录组数据库的神经信息学数据库。使用这个数据库,我们已经鉴定了数千个基因,这些基因被分类为各种功能类别,并与相关的细胞发育阶段同时表达。我们还通过对几个负责发育中小脑颗粒细胞不同细胞事件的鉴定基因(Cupidin、p130Cas、very-KIND、CAPS2)的功能特征分析,提出了小脑发育的分子机制。总之,小脑发育过程中的基因表达谱表明,小脑皮质回路的发育归因于复杂但协调的转录组。

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