The proposed research is designed as analytical and manipulative investigations of mechanisms critical to cell migration and nerve fiber outgrowth in patterning of the developing nervous system. The studies will focus on growth factors influencing these events during early stages of neurogenesis, and will examine the potential of these factors to enhance and guide later regenerative growth. The developing trigeminal (V) motor nucleus in the chick embryo will be used as a model system. For these studies, tissue culture techniques will be used to evaluate the role of the trigeminal ganlion and normal target tissue (jaw muscle) in providing trophic or directing effects on fiber outgrowth and somal translocation. Our previous in vivo studies have indicated the ganglion is vital to normal development of V motor nucleus, and our in vivo and in vitro studies suggest that muscle tissue plays a trophic or directing role during later developmental stages. Basal plate explants of the trigeminal region, taken before the onset of cell migration and nerve fiber outgrowth, will be cultured alone, with disaggregated ganglion tissue, with control neural tissue, with ganlia conditioned media, with whole ganglia plated in varying positions, and with appropriate and inappropriate muscle tissue. Explants from embryos at later developmental stages will also be grown alone and with ontogenetically sequenced ganglionic tissue or target musculature in order to examine the potential of these tissues to provide their trophic influences during later stages, and the capacity of the V motoneurons to respond to these influences during their subsequent development. These studies will be significant in analyzing previously unknown growth factors, and the capacity of these factors to direct both initial neurogenesis and later regenerative growth. Such analyses will contribute to an improved understanding of normal nervous system development and may provide insights which will have significance in remediation of nervous system damage.
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