Programmed cell death plays a central role in many diseases, including cancer and neurodegenerative disorders. Programmed cell death is also a critical process for proper patterning during development. The long-term goal of this project is to understand how programmed cell death is regulated during development. IAPs, inhibitor of apoptosis proteins, are a family of cellular inhibitors of apoptotic cell death. Drosophila IAP1 (Diap1) is a critical regulator of apoptosis during Drosophila development. Null mutations in diap1 result in extensive cell death during early embryogenesis, indicating that Diap1 must be present in most, if not all cells, to prevent apoptosis. The diap1 gene was originally called thread, named for the first mutation identified in the gene. The thread1 mutation is homozygous viable, and the only phenotypic effect is a disruption of branching in the antennal arista. The mechanisms controlling branch formation in the arista are not well understood. Preliminary studies indicate that thread1 mutants show excessive cell death restricted to the antennal imaginal disc during larval development. This suggests that there is a narrow window of development in which regulation of programmed cell death is essential to proper branch formation in the arista. The arista-specific phenotype seen in the thread1 mutant suggests that the mutation may disrupt thread expression only in the developing arista. Preliminary data indicate that the mutation is not in a protein-coding region. The goal of this proposed research is to determine the molecular nature of the thread1 allele and to determine how this mutation affects expression of the thread gene. The cis-regulatory elements affected by the mutation and the upstream signaling pathways controlling thread expression will be investigated. These findings will lead to a better understanding of the transcriptional regulation of IAPs, which may alter the threshold for induction of apoptosis. Furthermore, this work will provide insight into the role of programmed cell death in the development of branched organs.
