Fork head controls the timing and tissue selectivity of steroid-induced developmental cell death.
Cell death during Drosophila melanogaster metamorphosis is controlled by the steroid hormone 20-hydroxyecdysone (20E). Elements of the signaling pathway that triggers death are known, but it is not known why some tissues, and not others, die in response to a particular hormone pulse. We found that loss of the tissue-specific transcription factor Fork head (Fkh) is both required and sufficient to specify a death response to 20E in the larval salivary glands. Loss of fkh itself is a steroid-controlled event that is mediated by the 20E-induced BR-C gene, and that renders the key death regulators hid and reaper hormone responsive. These results implicate the D. melanogaster FOXA orthologue Fkh with a novel function as a competence factor for steroid-controlled cell death. They explain how a specific tissue is singled out for death, and why this tissue survives earlier hormone pulses. More generally, they suggest that cell identity factors like Fkh play a pivotal role in the normal control of developmental cell death.
Cao
Chike
C
Department of Biological Sciences, University of Arkansas, Fayetteville, AR 72701, USA.
Liu
Yanling
Y
Lehmann
Michael
M
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology / Q000254:growth & development*; D004441:Ecdysterone / Q000502:physiology*; D051858:Forkhead Transcription Factors; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors; D008018:Life Cycle Stages; D008954:Models, Biological; D009154:Mutation; D009479:Neuropeptides / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D012469:Salivary Glands / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
C102117:Br protein, Drosophila; D029721:Drosophila Proteins; D051858:Forkhead Transcription Factors; C108880:HID protein, Drosophila; D051034:Inhibitor of Apoptosis Proteins; D009479:Neuropeptides; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; C512745:fkh protein, Drosophila; C086973:rpr protein, Drosophila; D004441:Ecdysterone