A balance between the diap1 death inhibitor and reaper and hid death inducers controls steroid-triggered cell death in Drosophila.
The steroid hormone ecdysone directs the massive destruction of obsolete larval tissues during Drosophila metamorphosis, providing a model system for defining the molecular mechanisms of steroid-regulated programmed cell death. Although earlier studies have identified an ecdysone triggered genetic cascade that immediately precedes larval tissue cell death, no death regulatory genes have been functionally linked to this death response. We show here that ecdysone-induced expression of the death activator genes reaper (rpr) and head involution defective (hid) is required for destruction of the larval midgut and salivary glands during metamorphosis, with hid playing a primary role in the salivary glands and rpr and hid acting in a redundant manner in the midguts. We also identify the Drosophila inhibitor of apoptosis 1 as a survival factor in the larval cell death pathway, delaying death until its inhibitory effect is overcome by rpr and hid. This study reveals functional interactions between rpr and hid in Drosophila cell death responses and provides evidence that the precise timing of larval tissue cell death during metamorphosis is achieved through a steroid-triggered shift in the balance between the Drosophila inhibitor of apoptosis 1 and the rpr and hid death activators.
Yin
Viravuth P
VP
Department of Human Genetics and Howard Hughes Medical Institute, University of Utah School of Medicine, Salt Lake City, UT 84112-5331, USA.
Thummel
Carl S
CS
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000187:drug effects / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D051034:Inhibitor of Apoptosis Proteins; D007814:Larva / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008675:Metamorphosis, Biological / Q000187:drug effects; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D012330:RNA, Double-Stranded / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012469:Salivary Glands / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013256:Steroids / Q000494:pharmacology*; D013270:Stomach / Q000166:cytology / Q000187:drug effects
C111891:DIAP1 protein, Drosophila; C111892:DIAP2 protein, Drosophila; D029721:Drosophila Proteins; C108880:HID protein, Drosophila; D018840:HSP70 Heat-Shock Proteins; D051034:Inhibitor of Apoptosis Proteins; D009479:Neuropeptides; D012330:RNA, Double-Stranded; D012333:RNA, Messenger; D013256:Steroids; C086973:rpr protein, Drosophila