Drosophila Teratogenesis and the role of Hsp70

The general goal of this research is to understand the developmental consequences of heat stress and the adaptive significance of variation in expression of the major inducible heat-shock protein of Drosophila melanogaster, Hsp70. In collaboration with Dr. Martin Feder (University of Chicago), we study heat stress in the laboratory and in nature (where larvae infesting necrotic fruit can experience severe stress), transgenic and natural variation in the genes encoding Hsp70, and the advantages and disadvantages of Hsp70 expression. Most effort has been focused on examining natural populations and genetically engineered mutants to characterize the teratogenic effects of high temperature stress and the role of Hsp70 in blocking or repairing these effects. This research has demonstrated (a) differential sensitivity to induction of wing phenocopies among hsp70 mutants and natural populations varying in Hsp70 expression and thermotolerance and (b) differential adult locomotor impairment among hsp70 mutants previously exposed to pupal heat shock.

In collaboration with Dr. J. Steven deBelle (UNLV), another continuing project in this area is to understand the consequences of heat stress and olfactory enrichment on the development and function of the Drosophila mushroom body (MB), a highly conserved region of the insect brain responsible for associative learning. Normal development of MBs has been demonstrated in genetic, transgenic and ablation studies to be critical for cognitive function in Drosophila. Environment conditions greatly affect MB anatomy, with artificially enriched (versus deprived) olfactory and visual environments enhancing their development. Our hypothesis is that enrichment and stress oppositely affect behavior and brain genomic activity as they do MB anatomy, and that the effects of concurrent enrichment and stress on these parameters are counteractive. Specifically, we are examining the consequences of ecologically relevant variation in olfactory enrichment and thermal stress during development on (1) MB and general anatomy, (2) behavior, and (3) gene expression in flies. We have demonstrated that exposure to variation in temperature and chemical stressors disrupts Drosophila MB anatomy. We have replicated our initial study that showed a MB-specific response to heat shock treatments during development and are now examining (1) the influences of heat shock on MB anatomy at different stages of development, (2) the effects of heat shock on GFP expression driven in the MBs by different GAL4 drivers, and (3) memory and other behaviors in heat shocked flies. We have shown that MBs are sensitive to heat shock and reduced following treatment during all stages of larval and pupal development. Each type of Kenyon cell (born sequentially in different developmental stages) is reduced – either in number or in size. Our observations suggest that stress is probably exerting these effects on MB precursor neuroblasts or ganglion mother cells. Furthermore, heat-shocked flies with impaired MB development are poorly able to form paired memories of odor and electric shock, although they sense these stimuli as well as healthy flies.