# Génétique et Neurotransmission, Laboratoire LNCF, CNRS UPR 9013, 13402 Marseille Cedex 9, France , § Department of Biology, Gilmer Hall, University of Virginia, Charlottesville, VA 22903, USA,
Two enzymes are required for dopamine biosynthesis from its precursor tyrosine: dopa decarboxylase (DDC) and tyrosine hydroxylase (TH). In Drosophila melanogaster, dopamine is expressed both in the hypoderm, where it is required for sclerotization of the cuticle, and the CNS, where it is thought to act as a neurotransmitter. Our experiments are directed towards understanding the neural function of dopamine by selectively misexpressing the Tyrosine hydroxylase gene in the CNS. Drosophila TH mutants (pale, abbreviated ple) are characterized by an unpigmented cuticle and late embryonic lethality. We have found that pale mutant flies can be rescued with a transgene that contains a TH cDNA driven by an incomplete dopa decarboxylase promoter (pDdc/TH). This rescue is insertion site specific, presumably due to local enhancers near where the transgene has inserted. In one of the pDdc/TH ; ple transgenic lines, approximately 20-30% survive to adulthood with normally developed but lightly pigmented cuticles. These transgenic flies are weaker than wild-type flies, but they appear normal for locomotion, feeding and grooming. Immunostaining of pDdc/TH ; ple larval CNS with an antibody directed against dopamine shows a loss of dopamine in many dopaminergic neurons of the brain lobes. We are now conducting tests with these flies to determine the effect of loss of dopamine in these specific subsets of cells on neural development and behavior.