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 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.