Forebrain development is an extremely complex process that depends on the coordination of multiple molecular networks controlled by a relatively small group of transcription factors. Understanding of these genes, their downstream pathways and their spatial and temporal interactions is still far from clear, seriously limiting our knowledge of the molecular mechanisms of brain development and the causes of neurodevelopmental diseases. Our research will be aimed at deepening understanding of the molecular actions of one of such transcription factor, Pax6, during mouse diencephalic development with special attention to its interaction with the Shh pathway. We shall be following changes in gene expression profiles (by RNA-seq) in normal and Pax6 mutant cells (with or without Shh blockade treatment) and interrogating the data with bioinformatic methods. The outcomes expected from this aspect include identification of genes downstream of Pax6, the relationships between these genes and their putative interactions with the Shh pathway. In a second phase of the project, we shall test specific hypotheses on whether Pax6 regulates genes in the downstream networks through direct interactions (using ChIP and EMSA assays) and will correlate Pax6’s molecular actions with its cellular functions. This represents the first study of the diencephalon under this innovative and multidisciplinary approach.
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