Our long-term objective is to understand how genes control the specialization and patterning of body segments in Drosophila. Much of the work proposed in this application is focused on the homeotic gene spineless-aristapedia (ss), which specifies the identity of the distal antenna, and functions in the establishment of the tarsal primordium in each of the thoracic legs. ss encodes a bHLH PAS transcription factor that is the closest known homolog of the mammalian dioxin receptor. Our major objectives are to determine how ss is spatially regulated, and how its functions are modulated in the antenna and tarsus. Genes identified in a ss enhancer screen will be characterized to determine their roles in the regulation and modulation of ss function. Also, the cis-regulatory element responsible for ss expression in the tarsus will be dissected and tested for direct regulation by Distal-less, a master regulator of ventral appendage development. Experiments are also planned to determine the extent to which the functioning of the dioxin receptor and ss are conserved. A second major goal is to characterize 23 genes identified as enhancers of a loss-of-function allele of the pair-rule gene fushi tarazu (ftz). Any genes found to be specifically required for ftz expression or function will be targeted for characterization at the molecular level. Finally, a third major goal is to identify new genes involved in patterning adult abdominal segments. Loss-of-function and ectopic expression screens will be carried out to identify genes responsible for several different unexplained aspects of abdominal patterning. Additional goals are to test if hedgehog secretion is polarized in the abdominal epithelium, to test the role of cell adhesion in abdominal patterning, and to determine the null phenotypes for two mutations that cause ventral-to-dorsal transformations in the abdomen. The health significance of the proposed research is that it may lead to a better understanding of patterning in human development, and hence how congenital abnormalities arise. In addition, our work on ss promises to provide insights into the mechanisms by which dioxin and other aryl hydrocarbons exert toxicity in humans.
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