Dendrites represent the primary site of sysnapse formation in the vertebrate nervous system, and the size of the dendritic arbor restricts the number of synaptic inputs a neuron receives. Therefore, characterizing the mechanisms that control dendritic growth may provide insights as to how synaptic contacts are established and maintained not only during normal development and remodeling, but also in pathological states. Osteogenic protein -1 1 (OP-1) has recently been identified as a unique trophic factor that selectively induces dendrite formation in cultured embryonic sympathetic neurons. To establish the relevance of these in vitro observations to neuronal morphogenesis in situ, it will be necessary to determine if the temporal and spatial distribution of OP-1 is coincident with dendritic growth and to identify the cell type(s) that produce OP-1. Immunocytochemistry, immunoprecipitation, in situ hybridization, and RNase protection analyses of sympathetic ganglia, nerves, and target tissues will be employed to accomplish these objectives. Since preliminary data suggest that both local and target cells may provide OP-1 to sympathetic neurons, regulation of neuronal access to OP-1 via retrograde transport will be assessed. Finding that retrograde transport is a major means of delivering OP-1 to neurons has significant implications regarding mechanisms of dendritic atrophy in axonal lesioning or degeneration.
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