The proposed research is a continuation of ongoing studies of neuronal growth, development, and transmitter phenotypic expression. Using a combination of biochemical, immunocytochemical, and pharmacological techniques, we have defined factors governing embryogenesis in sympathetic and sensory neurons, the factors regulating peptide neurotransmitter phenotypic expression, and the role of intercellular communication in neuronal ontogeny. In particular, we have focused on defining the molecular mechanisms regulating development of the putative peptide neurotransmitters, substance P (SP) and somatostatin (SS). The present studies will examine neuron target interactions and the role of growth factors in mediating the effects of these interactions on neuronal phenotypic expression. More specifically, we hope to a) Examine the effects of a recently described peptide stimulating factor on SP and SS development in sensory, sympathetic, and striatal neurons in vivo, b) Define the effects of this growth factor on cholinergic development in striatal neurons in vivo and in culture, c) Define the role of SP and SS in regulating sympathetic, noradrenergic development, d) Examine interactions between the overlapping sensory, sympathetic, and parasympathetic innervations of the iris, e) Use the above information to understand processes governing neuronal phenotypic expression and interneuronal communication. It is hoped that these studies will elucidate mechanisms leading to abnormal neuronal development and indicate new therapeutic approaches to diseases of disordered neural development.
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