Unreaviling the up-stream events which lead to primordial germ cells death by alternative cell death, during drosophila embryonic development

In a recent study, we solved a two-decade old mystery; unraveling the alternative cell death (ACD) pathway of the Drosophila primordial germ cells (PGCs) during early embryogenesis (Tarayrah-Ibraheim et al., 2021). It has been known that during embryonic stages 10 and 13, about one-third of the PGCs fail to migrate to the gonads and are eliminated by cell death, but efforts to block this cell death by manipulating apoptosis, attempted by several groups, had all failed, suggesting divergence from the conventional apoptotic program. Significantly, we showed that PGC death is highly reminiscent of an ACD called parthanatos, demonstrating the first developmental paradigm of this ACD pathway. In short, parthanatos, which has been implicated as a main driver of Parkinson’s disease, is defined by activation of PARP-1, which leads to the translocation of AIF from the mitochondria to the nucleus, carrying with it a nuclease that cleaves and fragments the nuclear DNA. Significantly, we showed that in PGCs, this nuclease is the lysosomal of DNase II, which is absolutely required for PGC death. However, how this death is triggered in vivo remains unclear. Here, I will present our approach to address this question through isolation of the PGCs and subjection to scRNA-seq analysis, as well as initial results from this analysis.