The long term objective of this study is to understand the molecular mechanisms that cause some target genes to be induced by moderate concentrations of ecdysteroid while other target genes are induced only by much higher concentrations of the steroid. Although the developmental significance of the proper progression of moderate levels of ecdysteroid followed by high levels during insect metamorphosis has been established, the underlying mechanisms that allow different concentrations of the same hormone to evoke profoundly different developmental programs are not known. Striking similarities exist with the roles of moderate versus high levels of thyroid hormone during amphibian metamorphosis. The receptors for the metamorphic hormones in both insects and amphibians are nuclear receptors suggesting that the underlying mechanism of receptor action may be a broadly significant feature of nuclear receptors, including those that play critical roles in governing human development. The primary objective of the current study is to examine ecdysteroid regulation of target gene expression in Drosophila cell culture lines in order to characterize the mechanisms that allow different sets of target genes to be activated by different concentrations of the steroid. Specifically, target gene expression will be analyzed under a variety of hormone conditions and the composition of the ecdysteroid receptor complex on different target genes will be determined using in vivo crosslinking methods. One long-term goal of the project, although beyond the scope of the current proposal, is to extend the findings of the detailed promoter analysis begun here into analysis of target gene expression in the developing fly.
| Weber, Kenneth; Johnson, Nancy; Champlin, David et al. (2005) Many P-element insertions affect wing shape in Drosophila melanogaster. Genetics 169:1461-75 |
