This proposal is directed at understanding the regulation of a developmentally regulated gene in the fruit fly, Drosophila melanogaster. An additional focus of interest is to study a cluster of genes within which the gene is located. The gene codes for the enzyme dopa decarboxylase (DDC), an essential enzyme involved in metabolic pathways leading to cuticular hardening and neurotransmitter synthesis. The gene is subject to striking developmental regulation, and is hormonally regulated during at least part of the life cycle. We will study the regulation of this gene using a combination of molecular and classical genetic techniques. A high priority is the molecular definition and comparison of Ddc transcripts from different developmental stages and tissues, since the gene is probably expressed via different mechanisms at different developmental stages. We will examine regulatory steps in the expression of Ddc both in vivo and in organ culture systems. Mutant strains will be used to aid in the definition of sequences important in overall gene expression, and in specific developmental expression. Classical ligation experiments will be performed to assay for diffusible substances affecting Ddc expression. These studies are focussed on the study of a gene much like many genes involved in human development. We work on Drosophila because this organism offers many advantages in experimental approach over more complex higher organisms. The results of this study will be basic information on how developmentally regulated genes function, and should generate basic knowledge applicable to many higher organisms.
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