Physiological apoptosis of polar cells during Drosophila oogenesis is mediated by Hid-dependent regulation of Diap1.
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.
Cellular Dynamics and Development Department, Centre de Génétique Moléculaire (FRE 3144), Centre National de Recherche Scientifique, 1 ave de la Terrasse, Gif sur Yvette, France.
A
A
Khammari
F
F
Agnès
P
P
Gandille
A-M
AM
Pret
D000818:Animals; D017209:Apoptosis; D016827:CD8 Antigens / Q000378:metabolism; D061945:Caspase Inhibitors; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000502:physiology*; D005260:Female; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D009866:Oogenesis; D006080:Ovarian Follicle / Q000166:cytology / Q000378:metabolism; D010053:Ovary / Q000166:cytology / Q000502:physiology*; D034622:RNA Interference; D011994:Recombinant Proteins / Q000096:biosynthesis; D014764:Viral Proteins / Q000096:biosynthesis
D016827:CD8 Antigens; D061945:Caspase Inhibitors; D015816:Cell Adhesion Molecules, Neuronal; C111891:DIAP1 protein, Drosophila; D029721:Drosophila Proteins; C061565:Fas3 protein, Drosophila; C108880:HID protein, Drosophila; D051034:Inhibitor of Apoptosis Proteins; D009479:Neuropeptides; D011994:Recombinant Proteins; D014764:Viral Proteins; C400550:dark protein, Drosophila; C492234:p35 protein, Baculovirus; D020169:Caspases; C109171:drICE protein, Drosophila; C118731:dronc protein, Drosophila