RUI: Tissue-Specific Gene Regulation in Drosophila

Mount Holyoke College, South Hadley MA

Investigators

Abstract

Steroid hormones control a wide range of physiological and developmental processes in higher organisms, acting in conjunction with receptor proteins to regulate the stage- and tissue-specific transcription of target genes. The study of steroid receptor genetics and biochemistry has led to enormous advances in our understanding of how steroids activate gene transcription. Remarkably, a single hormone appears to be capable of inducing extremely different responses, depending on cellular and temporal context. Although much is understood about how steroid receptors control transcription in cultured mammalian cells, little is understood about how these effects on gene expression result in the dramatic stage- and tissue-specific developmental changes associated with steroid hormone action. This project makes use of the fruit fly, Drosophila melanogaster, to examine how steroid-induced changes in gene expression control specific cellular responses during development. Pulses of the steroid 20-hydroxyecdysone (ecdysone) trigger genetic regulatory hierarchies that direct both destruction of tissues by programmed cell death, and morphogenesis (the formation of structures). This project focuses on the roles of nuclear receptor beta-FTZ-F1 and the ecdysone receptor in controlling the stage- and tissue-specific expression of a set of ecdysone-inducible "early" genes, including BR-C, E74A, E75A and E93. In this examination of the molecular mechanism underlying these gene regulatory phenomena, particular attention is paid to the regulation of E93. E93 is precisely regulated by ecdysone in dying cells, where it induces a programmed cell death response. In certain tissues, such as the larval salivary gland, the regulation of E93 by ecdysone depends on beta-FTZ-F1, which appears to provide E93 with the competence to respond to the hormone. Goals of this project are to address how members of the nuclear receptor superfamily regulate the stage- and tissue-specific expression of E93, as well as BR-C, E74A, and E75A during development, and to shed light on the mechanisms by which steroid hormones elicit distinct biological responses.