Identification of Transcription Factor Networks in Mammalian Brain Development

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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.