Identification of Transcription Factor Networks in Mammalian Brain Development

哺乳动物大脑发育中转录因子网络的鉴定

• 批准号: RGPIN-2017-04912
• 负责人: Goldowitz, Daniel
• 金额: $ 2.04万
• 依托单位: University of British Columbia
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=629056
• 关键词: Identification; Transcription; Factor; Networks; Mammalian

The mammalian brain is a highly complex biological system and understanding how the brain develops is a daunting task. Determining the underlying molecular processes that are involved in brain development can be a strong first step toward this goal. One region of the brain, the cerebellum, which is mainly involved with the coordination of motor function, has been an excellent model system to study as it is composed of a limited number of cell types that have a simple layered architecture. Furthermore, the cerebellum is easily accessible for dissection throughout its development. In the past funding period, we have built two extensive time-series transcriptome data sets that cover 12 points in time during early embryogenesis through to early postnatal life. The first is an Illumina-based data set that we call CbGRiTS (Cerebellar Gene Regulation in Time and Space). The second used a new technology developed by our collaborators at the RIKEN OMICS Institute called CAGE (Cap Analysis of Gene Expression), which enables us to catalogue the initiation sites for most RNA species. This approach to map these sites and record their usage at a genomic scale synergizes with CbGRiTS and our expertise in studying cerebellum development. Three Objectives will take a comprehensive analysis of CAGE and CbGRiTS data that will permit the identification of strong candidate genes and novel elements of gene regulatory networks governing the development of the cerebellum. In this way we can discover important, new genes that control developmental processes in the cerebellum.

哺乳动物的大脑是一个高度复杂的生物系统，了解大脑如何发育是一项艰巨的任务。确定参与大脑发育的潜在分子过程可能是实现这一目标的第一步。大脑的一个区域，小脑，主要涉及运动功能的协调，一直是一个很好的模型系统来研究，因为它是由有限数量的细胞类型，具有简单的分层结构。此外，小脑在整个发育过程中易于解剖。在过去的资助期间，我们建立了两个广泛的时间序列转录组数据集，涵盖了早期胚胎发育到早期出生后生命的12个时间点。第一个是基于Illumina的数据集，我们称之为CbGRiTS（时间和空间中的小脑基因调控）。第二项研究使用了我们在RIKEN OMICS研究所的合作者开发的一种新技术，称为CAGE（基因表达的帽分析），该技术使我们能够对大多数RNA物种的起始位点进行编目。这种在基因组规模上绘制这些位点并记录其使用情况的方法与CbGRiTS和我们在研究小脑发育方面的专业知识协同作用。三个目标将采取CAGE和CbGRiTS数据的全面分析，这将允许确定强有力的候选基因和新的基因调控网络的元素，控制小脑的发展。通过这种方式，我们可以发现控制小脑发育过程的重要的新基因。