The long-term objective of the proposed research is to understand development of the mushroom bodies, structures important for learning and memory in Drosophila melanogaster. Toward this goal, I am studying the function of the novel protein DACHSHUND. Our interest in the dachshund phenotype stems from its abnormal mushroom body structure, although mutant flies also have reduced, roughened eyes and short legs and die shortly after eclosion. Dachshund is the first cloned gene to be associated with mushroom body structural defects. To dissect dachshund's role in mushroom body development, I am proposing three specific aims: (1) Determine if the mushroom body structural defect in dac mutants is cell autonomous. (2) Ascertain when DACHSHUND is required for proper mushroom body formation. (3) Assess dachshund's role in mushroom body fate determination. Dachshund has previously been shown to direct eye formation when ectopically expressed in imaginal discs. The presence of dachshund vertebrate homologs suggests conservation of a molecular and developmental pathway through evolution. If this is indeed the case, studying dachshund's role in mushroom body development could elucidate developmental principles at work in the mammalian brain. Such conservation would not be surprising, since the biochemical pathways involved in learning have been conserved from Aplysia to Drosophila to mammals. If a developmental pathway for structures involved in learning has also been conserved, studying dachshund may help us understand cognitive deficits in humans.
