Steroid hormones are critical regulators of programmed cell death in all higher organisms. In spite of their central role in this process, however, the mechanisms by which steroid hormones regulate cell death remain unclear. Here, a forward genetic strategy is proposed to study a dramatic example of steroid-triggered cell death: the massive and rapid destruction of larval tissues during Drosophila metamorphosis in response to the steroid hormone ecdysone. To this end, a simple assay has been developed to monitor larval salivary glands in living animals. Mutations that disrupt larval salivary gland cell death will be selected and only those mutations that result in a block of the death response, rather than those that disrupt the ecdysone signal, will be further characterized. A genetic strategy has never been used to study hormone-triggered cell death in any organism. These studies will provide not only a better understanding of the hormonal regulation of programmed cell death, but will also serve as a model system for understanding how systemic hormonal signals are refined into stage- and tissue-specific biological responses during development. In addition, further characterization of apoptotic signaling pathways will allow a better understanding of autoimmune diseases, neurodegenerative disorders, and other diseases that result from misregulation of programmed cell death.
