Germline Cell Death Is Inhibited by P-Element Insertions Disrupting the dcp-1/pita Nested Gene Pair in Drosophila

Abstract

Germline cell death in Drosophila oogenesis is controlled by distinct signals. The death of nurse cells in late oogenesis is developmentally regulated, whereas the death of egg chambers during mid-oogenesis is induced by environmental stress or developmental abnormalities. P-element insertions in the caspase gene dcp-1 disrupt both dcp-1 and the outlying gene, pita, leading to lethality and defective nurse cell death in late oogenesis. By isolating single mutations in the two genes, we have found that the loss of both genes contributes to this ovary phenotype. Mutants of pita, which encodes a C2H2 zinc-finger protein, are homozygous lethal and show dumpless egg chambers and premature nurse cell death in germline clones. Early nurse cell death is not observed in the dcp-1/pita double mutants, suggesting that dcp-1+ activity is required for the mid-oogenesis cell death seen in pita mutants. dcp-1 mutants are viable and nurse cell death in late oogenesis occurs normally. However, starvation-induced germline cell death during mid-oogenesis is blocked, leading to a reduction and inappropriate nuclear localization of the active caspase Drice. These findings suggest that the combinatorial loss of pita and dcp-1 leads to the increased survival of abnormal egg chambers in mutants bearing the P-element alleles and that dcp-1 is essential for cell death during mid-oogenesis.

ER stress protects from retinal degeneration

“…This anti‐apoptotic effect is dose dependent, as complete loss of ninaA lead to further protection (Figure 1D–F, K; Supplementary Table 1). To determine whether resistance to PRC death observed in ninaA mutants is specific to rpr ‐induced cell death, ninaA mutant retinas were submitted to the ectopic expression of Drosophila p53 ( dp53 ) or death caspase‐1 ( dcp‐1 , a Drosophila homolog of caspase‐3) (Brodsky et al , 2000; Laundrie et al , 2003). Similarly to rpr , retinas mutant for ninaA were resistant to cell death induced by the ectopic expression of dp53 as well as dcp‐1 (Figure 1, G–J, K; Supplementary Table 1).…”

Murder on the Ovarian Express: A Tale of Non-Autonomous Cell Death in the Drosophila Ovary

“…Additional evidence for the role of the FCs in promoting germline death comes from a recently published RNAi screen of the kinome that identified several genes that lead to an "undead" phenotype in which the germline remains intact, while the FC layer dies away [86]. The "undead" egg chamber phenotype was previously described in flies lacking the executioner caspase Dcp-1 or overexpressing the apoptosis inhibitor DIAP1 in the germline [30,74,87]. When any of the kinase genes Taf1, ksr, Wnk, vari, CG7766, CG7156, Ask1, tkv, RIOK1, or SNF4Agamma were knocked down in the FCs, the undead phenotype was observed, demonstrating that some signal from the FC must play a role in the death of the germline [86].…”

“…Although several environmental perturbations can induce cell death during midoogenesis, the best characterized stimulus is starvation [37,73]. Starvation-induced cell death has been categorized as primarily apoptotic due to the morphological characteristics and its requirement for the effector caspase Dcp-1 [32,74]. One noteworthy feature of starvation-induced egg chamber death is its synchronicity; rather than each NC degrading at its own rate, the entire germline undergoes the same processes simultaneously (Figure 3) [19,30].…”

Understanding Developmental Cell Death Using Drosophila as a Model System

“…During the later stages of oogenesis, nurse cells expel cytoplasm-containing maternal mRNAs, organelles, and proteins into the maturing oocyte, leading to PCD of nurse cells while causing no detrimental effects to the attached oocyte [99,100]. Though there is an established apoptotic role in the removal of egg chambers during germarium and mid-oogenesis stages, recent findings suggest that this process is also triggered by nutrient deprivation [101,102]. Under starvation conditions, knockdown of Atg1 and Atg7, as well as Dcp-1 effector caspase mutants, fail to activate autophagy, causing a persistence of egg chambers [101].…”