Grant: Operating Grant

Normal nervous system function requires the generation of an enormous diversity of neurons during development. Differences in neuronal identity and function depend upon the repertoire of genes expressed in different neurons. We are examining how differences in neuronal gene expression are specified by the intersection of 1) transcription factors intrinsic to the neuron, with 2) extrinsic signals that neurons receive from the target cells that they innervate. Using the fruit fly, Drosophila melanogaster, as our model, we have found that the signals that neurons receive from their target cells activate different gene expression profiles in different neurons. Because this is a conserved mechanism for neuronal differentiation, we can take advantage of the powerful molecular genetic technologies of Drosophila to rapidly derive novel insight into how these mechanisms operate in humans. Disruptions in transcription factor function has been linked to congenital disorders and disruption of target-derived signal trafficking has been strongly implicated in neurodegenerative disorders. Our studies will provide a mechanistic understanding of how these factors control neuronal function. This will greatly improve our understanding of the aetiology of diseases where these factors have been disrupted