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

Abstract

Although much has been learned in recent years about the apoptotic machinery, the mechanisms underlying survival and death choices during development of metazoans remain less clearly understood. During early oogenesis in Drosophila, a small excess in the number of specialized somatic cells, called polar cells (PCs), produced at follicle extremities is reduced to exactly two cells through apoptosis by mid-oogenesis. We have found that PCs destined to die first lose their apical contacts and then round up and shrink progressively until they disappear. Caspases are activated only once the cells have begun to shrink, suggesting that they are implicated in this part of the process, but not in the initial loss of cell polarity. Loss-of-function analyses based on mutant, clonal and RNAi approaches show that among the RHG family of pro-apoptotic factors, Hid is specifically necessary for PC apoptosis, as well as the initiator caspase Dronc and its adaptor Dark/Apaf-1, and likely several effector caspases, in particular Drice. In addition, we show that Hid protein and transcripts accumulate specifically in PCs destined to die, while the anti-apoptotic factor Diap1 is downregulated in these cells in a hid-dependent manner. Therefore, our results implicate the Hid-Diap1 module as an important regulatory point in a developmental case of apoptosis.

JAK/STAT autocontrol of ligand-producing cell number through apoptosis

“…1C) (Khammari et al, 2011). Expression of a UAS-updRNAi construct (VDRC3282) in PCs led to strong reduction of Upd protein accumulation from stage 2 (supplementary material Fig.…”

“…The enhancer trap updGal4 was used to target PCs specifically (Khammari et al, 2011). fruitlessGal4 (Boquet et al, 2000) (whose ovarian expression pattern is first characterised in this study) was used to target expression in terminal follicle cells except PCs.…”

“…1A). During early oogenesis, PCs are produced in excess (three to six cells) and supernumerary PCs are eliminated by apoptosis, such that only a pair of PCs survive at each extremity in 100% of follicles as of mid-oogenesis (stage 5 follicles) (Besse and Pret, 2003;Khammari et al, 2011). We have identified the components of the apoptosis machinery specifically responsible for PC apoptosis (Fig.…”

“…Restriction of PC number to two is physiologically necessary for PC organiser function, as the presence of excess PCs during late oogenesis, produced by blocking apoptosis, leads to defects in BC migration and stretch cell morphogenesis (Besse and Pret, 2003;Khammari et al, 2011).…”

“…Although there have been great advances in understanding the molecular mechanisms that lead to caspase activation and consequent apoptosis, how the cell death machinery is activated in vivo during development is still poorly understood. Drosophila ovarian polar cells (PCs) have emerged as an exquisite and relatively simple model to unravel the mechanisms by which apoptosis is induced in a physiological context during development (Besse and Pret, 2003;Vachias et al, 2010;Khammari et al, 2011). PCs are specialised somatic cells located at each extremity, anterior and posterior, of maturing ovarian follicles, where they are embedded within the monolayered follicular epithelium (Fig.…”