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，了解大脑是如何发育的是一项艰巨的任务。确定参与大脑发育的潜在分子过程可能是迈向这一目标的有力的第一步。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，因为它由有限的细胞类型组成，具有简单的分层结构。此外，小脑在整个发育过程中很容易进行解剖。在过去的资助期间，我们已经建立了两个广泛的时间序列转录组数据集，涵盖了从早期胚胎发育到出生后早期的12个时间点。第一个是基于Illumina的数据集，我们称之为CbGRiTS(时空中的小脑基因调控)。第二个使用了我们在RIKEN OMICS研究所的合作者开发的一项新技术，称为CAGE(基因表达的上限分析)，它使我们能够对大多数RNA物种的起始点进行编目。这种绘制这些位置图并在基因组规模上记录它们使用情况的方法与CbGRiTS和我们在研究小脑发育方面的专业知识相结合。三个目标将对CAGE和CbGRiTS数据进行全面分析，以识别控制小脑发育的强大候选基因和基因调控网络的新元素。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。

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.