Are biogenic amines involved in ovary morphogenesis? S.A. Sedore , R. Andretic , J. Hirsh , C. Cronmiller. Biology, University of Virginia, Charlottesville, VA.

   Oogenesis in Drosophila is a process that utilizes many of the same signaling pathways and cues that participate in other developmental events in the life of the fly. Recent studies have implicated the modulation of biogenic amine levels in certain morphogenetic events, such as gastrulation in embryogenesis. We are interested in the role of biogenic amines in oogenesis. Our data suggest a model that connects the levels of biogenic amines and their precursors with follicle formation.
   Drugs such as cocaine and fluoxetine are known to bind and inhibit monoamine transporters in Drosophila, resulting in an increase in biogenic amines in the synaptic cleft. Feeding cocaine to flies results in subtle behavioral abnormalities and, in a dose-dependent manner, in morphological defects in oogenesis. Among these defects are compound follicles, long interfollicular stalks, and improper migration of somatic epithelial cells. Other drugs that block monoamine transporters and alter the levels of biogenic amines in the synaptic cleft include fluoxetine (the active ingredient in Prozac), mazindol, and imipramine. We have administered these drugs to flies and found that they also have a pronounced effect on oogenesis. Finally, we have fed tyramine to females and found aberrant oogenesis phenotypes that are clearly different than those that result from blocking the monoamine transporters. Defects associated with tyramine feeding typically show a general loss of somatic cells as a follicle matures. Since tyramine is a precursor of octopamine in flies, the involvement of biogenic amines and their biosynthetic pathways in ovary morphogenesis may be complex. We are still characterizing and quantifying these varied phenotypes and determining the specificity of these drugs' effects on ovary morphogenesis.