Cell death duringDrosophila melanogasterearly oogenesis is mediated through autophagy

Abstract

Autophagy is a physiological and evolutionarily conserved process maintaining homeostatic functions, such as protein degradation and organelle turnover. Accumulating data provide evidence that autophagy also contributes to cell death under certain circumstances, but how this is achieved is not well known. Herein, we report that autophagy occurs during developmentally-induced cell death in the female germline, observed in the germarium and during middle developmental stages of oogenesis in Drosophila melanogaster. Degenerating germline cells exhibit caspase activation, chromatin condensation, DNA fragmentation and punctate staining of mCherry-DrAtg8a, a novel marker for monitoring autophagy in Drosophila. Genetic inhibition of autophagy, by removing atg1 or atg7 function, results in significant reduction of DNA fragmentation, suggesting that autophagy acts genetically upstream of DNA fragmentation in this tissue. This study provides new insights into the mechanisms that regulate cell death in vivo during development.

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

“…81,82 Interestingly, genetic inhibition of autophagy by removing the function of autophagy genes ATG1 and ATG7 results in decreased levels of DNA fragmentation in region 2 of the germarium compared to wild type. 83,86 These data suggest that autophagy can act upstream of apoptosis in the Drosophila germarium.…”

“…77 Fourteen stages of oogenesis have been described of egg chambers. 83,86,[89][90][91] Although autophagy is suggested to promote cell death of individual cells in the egg chambers, the resources generated from cell death promote better conditions for the physiology of the ovary and the whole fly in general, finally resulting in cell survival. A similar example is the autophagic cell death of the salivary gland in Drosophila during metamorphosis, a life stage in which the fly does not eat and must develop adult structures in the absence of external nutrient resources.…”

“…[82][83][84][85][86] Cell death in the germarium increases after nutrient deprivation and environmental stress, 82,87 and therefore is thought to serve as a "checkpoint" mechanism to maintain the proper number of follicle cells that are needed to encapsulate the germline cyst during the beginning of oogenesis. 81,82 Interestingly, genetic inhibition of autophagy by removing the function of autophagy genes ATG1 and ATG7 results in decreased levels of DNA fragmentation in region 2 of the germarium compared to wild type.…”

Caspase involvement in autophagy

“…In addition to these examples, Drosophila and mammalian oogenesis also share the degradation of supporting nurse cells by PCD, which promotes the growth and maturation of oocytes [107]- [109]. In nurse cells the effector caspase Dcp-1 (the Drosophila homolog to caspase-3) and its upstream inhibitor of apoptosis dBruce were first observed to regulate autophagic flux, which contributed in turn to ovarian PCD [110].…”

Oocyte destruction is activated during viral infection

“…However, cell biological mechanisms that control oocyte loss appear to be conserved with lower organisms like the fruit fly Drosophila melanogaster . For example, both mammalian ovarian follicles and insect egg chambers degenerate when specific apoptotic (Mazzalupo and Cooley, 2006;Nezis et al, 2002;Peterson et al, 2003;Tilly, 1998), autophagic (Escobar et al, 2008;Hou et al, 2008;Lobascio et al, 2007;Nezis et al, 2009Nezis et al, , 2010, and chromatin-degrading (Bass et al, 2009) pathways are activated. Moreover, complete degeneration and oocyte ''corpse'' removal is achieved by the phagocytosis of adjacent dead and dying cells by follicle cells in insects (Mazzalupo and Cooley, 2006) and granulosa cells in mammals (Inoue et al, 2000).…”