Grant: Operating Grant

Understanding how the nervous system develops normally, as well as abnormally in hereditary diseases, requires an understanding of the genes that are critical for brain development. Furthermore, repairing the diseased or damaged nervous system will ultimately require manipulating the expression of these genes. The zebrafish has emerged as a leading model for studies of vertebrate (and by extension human) developmental genetics because of the ease in manipulating and studying their embryos. Our group has defined key elements of the circuitry in the embryonic zebrafish spinal cord that are conserved across species. It is hypothesized that the cellular concentration of chloride ions is important for regulating the generation of neurons and development of connections between them in neural circuits. To directly test the role of chloride signaling, we propose to manipulate gene expression in the zebrafish embryo in order to alter the chloride ion concentration during development of the spinal cord circuitry. We will then examine the consequences of these manipulations by studying neural development and a model for peripheral neuropathy. Based on the mechanisms discovered in zebrafish embryos, we will test gene activities in stem cells from the adult mouse brain to determine the potential of regulating the production of new adult neurons.