The Drosophila caspases Strica and Dronc function redundantly in programmed cell death during oogenesis

Abstract

Programmed cell death (PCD) in the Drosophila ovary occurs either during mid-oogenesis, resulting in degeneration of the entire egg chamber or during late oogenesis, to facilitate the development of the oocyte. PCD during oogenesis is regulated by mechanisms different from those that control cell death in other Drosophila tissues. We have analyzed the role of caspases in PCD of the female germline by examining caspase mutants and overexpressing caspase inhibitors. Imprecise P-element excision was used to generate mutants of the initiator caspase strica. While null mutants of strica or another initiator caspase, dronc, display no ovary phenotype, we find that strica exhibits redundancy with dronc, during both mid-and late oogenesis. Ovaries of double mutants contain defective mid-stage egg chambers similar to those reported previously in dcp-1 mutants, and mature egg chambers with persisting nurse cell nuclei. In addition, the effector caspases drice and dcp-1 also display redundant functions during late oogenesis, resulting in persisting nurse cell nuclei. These findings indicate that caspases are required for nurse cell death during mid-oogenesis, and participate in developmental nurse cell death during late oogenesis. This reveals a novel pathway of cell death in the ovary that utilizes strica, dronc, dcp-1 and drice, and importantly illustrates strong redundancy among the caspases. The Drosophila caspases include three initiators with long prodomains -dronc (Drosophila Nedd-2-like caspase), dredd (Death-related ced-3/Nedd2-like) and strica, and four effectors -dcp-1 (death caspase-1), drice (Drosophila ice), damm and decay.

Physiological apoptosis of polar cells during Drosophila oogenesis is mediated by Hid-dependent regulation of Diap1

“…Among Dredd, Dronc and Strica, which resemble inititator caspases, 22 Dronc is specifically required for many of the known developmental cell death programs, with specific exceptions, as well as in radiation-induced apopotosis 15,16,23 along with the adaptor protein, Apaf-1/Dark. 18,24,25 Our analysis of dronc and dark null mutations indicates that both are necessary for PC apoptosis cell autonomously in PCs destined to die.…”

Autophagy and its physiological relevance in arthropods: Current knowledge and perspectives

“…81 Drosophila caspases Drice, Dcp-1, Dronc and Strica play a minor role in nurse cell death during late oogenesis, 106,107 suggesting that nonapoptotic forms of cell death also function in dying nurse cells during late oogenesis. Autophagy participates in this cell death process, functioning cooperatively with apoptosis for the most efficacious elimination of the degenerated nurse cells in several species.…”

Apoptotic mechanisms during competition of ribosomal protein mutant cells: roles of the initiator caspases Dronc and Dream/Strica

“…Although not individually required, initiator caspases might act redundantly in competitive apoptosis of Rp/+ cells. Although the dronc, dream and dredd triple mutant genotype has been constructed previously, 53 severe viability and fertility effects were encountered when combining caspase mutations with Minute backgrounds. An alternative inducible RNAi approach was undertaken (Figure 7).…”

“…Dream/ strica and Dronc are also required redundantly for nurse cell death during oogenesis and the programmed elimination of certain peptidergic neurons from the CNS during pupariation. 53,59 Further characterization of mechanisms of Dream/Strica activation may be revealing concerning the induction of competitive apoptosis by interactions between wild-type and Rp/+ cells.…”