Molecular genetics of odor reception and development in Drosophila

The field of olfaction poses a number of interesting questions, concerning development of the system, mechanisms of receptor-ligand interactions, modes of information encoding, signal transduction and processing. Drosophila melanogaster possesses a unique combination of features that make it an ideal model system for studying olfaction. In this thesis I describe two studies conducted in the area of the Drosophila olfaction. The first study is dedicated to characterization of Drosophila odor receptor (Or) genes and to investigation of how the molecular map of the peripheral olfactory system, defined by the expression of odor receptors, is integrated with the cellular map of distinct functional classes of olfactory receptor neurons. Through genetic and molecular analysis of three Or genes, Or22a, Or22b, and Or47a I demonstrate that individual receptors map to individual neuronal classes, and establish a correspondence between receptors, neurons and odors. Genetic analysis of a mutant lacking Or22a and Or22b , along with transgenic rescue experiments, provides direct evidence that a Drosophila Or gene, Or22a, is required in vivo for normal odor detection. I also investigate the possibility of a developmental role for Or genes in axonal pathfinding and demonstrate that axons of olfactory receptor neurons navigate correctly to their targets in the brain when the receptor genes normally expressed in them are missing or substituted by different Or genes.; In the second part, I describe the characterization of the Drosophila olfactory behavioral mutant dare. The dare gene encodes adrenodoxin reductase, an enzyme whose homolog in mammals plays a key role in biosynthesis of steroid hormones. Through genetic and molecular analysis of dare, I provide evidence that strongly supports a role for dare in synthesis of ecdysteroids, the insect steroid hormones, suggesting a conservation of steroidogenic pathways between mammals and insects. I demonstrate requirements for dare in the processes of molting, pupariation, oogenesis, eye development, nervous system maintenance, and olfactory behavior. Roles for ecdysteroids in nervous system maintenance and in insect olfaction have not previously been described.