Identification of Transcription Factor Networks in Mammalian Brain Development

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。我们的计划是建立在我们以前的工作和与日本RIKEN研究所基因组研究人员的现有合作基础上。 我们已经建立了一个广泛的时间序列转录组数据集，涵盖了从早期胚胎发生到出生后早期的12个时间点。RIKEN的研究人员开发了一种名为CAGE（基因表达帽分析）的新技术，该技术使科学家能够对基因表达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我们在研究小脑发育方面的专业知识协同作用。我们与RIKEN的研究人员一起，成功地在小脑发育期间以24小时的间隔创建了大量基因的表达读数。对小脑CAGE数据的综合分析将允许识别控制小脑发育的基因调控网络。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。我们还建立了一个基于互联网的数据库，名为GbGRiTS（时间和空间中的小脑基因调节），该数据库将托管所有科学数据，以促进研究大脑发育的科学家之间的协作与合作。目前的提案不仅突出了尖端基因组技术的使用，还为学生和年轻科学家提供了极好的培训机会，并促进了加拿大科学家与日本世界知名的RIKEN研究人员的合作。

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 the 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. Our plan is to build on our previous work and on an existing collaboration with the genomic researchers at the RIKEN Institute in Japan. We have built an extensive time-series transcriptome data set that covers 12 points in time during early embryogenesis through to early postnatal life. RIKEN researchers have developed a new technology called CAGE (Cap Analysis of Gene Expression), which enables scientists to catalogue the initiation sites for gene expression. This approach to map these sites and record their usage at a genomic scale synergizes with our expertise in studying cerebellum development. Together with the researchers at RIKEN we have successfully created expression readouts of large numbers of genes at 24 hour intervals during cerebellum development. Comprehensive analysis of cerebellum CAGE data will permit the identification of gene regulatory networks governing the development of the cerebellum. In this way we can discover important, novel genes that control developmental processes in the cerebellum. We also have built an internet-based database called CbGRiTS (Cerebellar Gene Regulation in Time and Space), which will host all of the scientific data to facilitate collaboration and cooperation among scientists studying brain development. The current proposal not only highlights the use of cutting-edge genomic technology, but also provides excellent training opportunities for students and young scientists and promotes collaboration of Canada-based scientists with world-renowned RIKEN researchers in Japan.