A requirement for caspases during programmed cell death in Drosophila oogenesis.

摘要

Programmed cell death (PCD) is a highly conserved process utilized during development to eliminate dangerous, damaged or excessive cells. PCD is regulated in part by a family of cysteine proteases known as caspases. In this study we utilized the Drosophila ovary as a model system to better understand the role that caspases play in PCD during development. Cell death can occur in the ovary as a checkpoint during midoogenesis, or to facilitate the development of the oocyte late in oogenesis. Loss of function phenotypes were generated and examined for six of the seven Drosophila caspases. In addition, the roles of two caspase inhibitors were analyzed through overexpression studies.; While most PCD in Drosophila occurs through the activation of the caspases Drone and Drice, we have uncovered a novel pathway responsible for cell death in the ovary. The effector caspase dcp-1 was found to be required for cell death of the gennline during mid-oogenesis, and the initiator caspases strica and dronc act redundantly during this stage. The Drosophila ovary also utilizes much of the same machinery during late oogenesis. All of the germline cells except for the oocyte normally degenerate by the end of oogenesis. However, strica; dronc and dcp-1; drice double mutants result in the persistence of these cells in up to 44% of mature egg chambers. The partial phenotype during late oogenesis indicates the involvement of caspases as well as a caspaseindependent pathway in the death of the female germline.; In addition, we have identified a novel mutation in microtubule star (mts), which encodes a catalytic subunit of protein phosphatase 2A. mts mutants are missing large segments of the wings, display a decrease in antennal branching and exhibit patches of rough tissue in the eyes. This is likely the result of an increase in apoptosis in the larval imaginal discs, indicating that mts acts as a negative regulator of cell death.; Based on the results of this study we now have a better understanding of the critical roles that caspases and the cell death machinery play in the development of Drosophila.