EMBRYONIC DEVELOPMENT OF EPINERGIC NEURONS IN BRAIN

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Epinergic neurons express specific enzymes required for the synthesis of epinephrine. The proposed studies will investigate the embryonic and postnatal differentiation of epinergic neurons in the rat brainstem and epinergic fibers in spinal cord and hypothalamus. In addition, possible hormonal influences on the development of epinergic phenotypic markers will be studied in vivo and in vitro. Immunocytochemistry, autoradiography, high-performance liquid chromatography, radioenzymatic assay and tissue culture will be combined to provide morphological and biochemical descriptions of epinergic differentiation. Specifically, the proposed studies seek to 1) define the temporal relationships between neurogenesis and epinergic phenotypic expression in neural tube and neural crest derivatives, 2) investigate the phenomenon of transient neurotransmitter expression in the brain, 3) describe the development of epinergic fibers in spinal cord and hypothalamus, 4) compare central to peripheral epinergic cells with respect to possible regulation by glucocorticoids, 5) elucidate possible transplacental effects of glucocorticoids on epinergic development in the fetal brain and spinal cord, 6) investigate expression of peptidergic phenotypes in epinergic neurons, and 7) study factors which influence the in vitro development of epinergic neurons in long-term explant cultures of embryonic medulla oblongata. These studies address fundamental issues in developmental biology and neuroscience concerning the processes involved in cell determination, specificity and differentiation. Elucidation of factors involved in neurotransmitter expression and development in brain and the possible role of hormones as extracellular influences, may, in the future, lead to an understanding of loci where changes in the milieu of the developing neuron produces aberrant development. In turn, this may contribute to an understanding of birth defects in the human and ultimately to therapeutic manipulation of processes involved in neuronal differentiation.