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

• Published in: Cell death and differentiation 2011-05, Vol.18 (5), p.793-805
• Main Authors: Khammari, A, Agnès, F, Gandille, P, Pret, A-M
• Format: Article
• Language: English
• Subjects: 631/136/2434/1706; 631/208/200; 631/80/82/23; 692/698/690/1520; Animals; Apoptosis; Biochemistry; Biomedical and Life Sciences; Caspase Inhibitors; Caspases - genetics; Caspases - metabolism; CD8 Antigens - metabolism; Cell Adhesion Molecules, Neuronal - metabolism; Cell Biology; Cell Cycle Analysis; Cell death; Drosophila melanogaster - cytology; Drosophila melanogaster - physiology; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Female; Follicles; Inhibitor of Apoptosis Proteins - genetics; Inhibitor of Apoptosis Proteins - metabolism; Insects; Kinases; Life Sciences; Neuropeptides - genetics; Neuropeptides - metabolism; Oogenesis; Original Paper; Ovarian Follicle - cytology; Ovarian Follicle - metabolism; Ovary - cytology; Ovary - physiology; Physiology; Proteins; Recombinant Proteins - biosynthesis; RNA Interference; Stem Cells; Viral Proteins - biosynthesis
• ISSN: 1350-9047; 1476-5403
• DOI: 10.1038/cdd.2010.141

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.