Genetic analysis of Drosophila steroid-triggered cell death

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Title Genetic analysis of Drosophila steroid-triggered cell death
Publication Type dissertation
School or College School of Medicine
Department Human Genetics
Author Yin, Viravuth Pho
Date 2005-08
Description Developmental programmed cell death plays a central role in metazoan development. Among other key death inducing signals, small lipophilic hormones provide an indispensable cue for the precise temporal and spatial elimination of cells and tissues. In Drosophila, two sequential pulses of the steroid hormone ecdysone direct the stage-specific death of larval tissues during metamorphosis. A late larval ecdysone pulse triggers the destruction of the larval midgut while the salivary glands are degraded in response to the prepupal ecdysone pulse, ~12 hours later. The destruction of the larval tissues is accompanied by classic hallmarks of apoptosis, including acridine orange staining, DNA fragmentation and caspase activation. Ecdysone triggers the death of these obsolete tissues through a two-tier genetic hierarchy, which culminates in the coordinate transcriptional induction of key death activators, reaper (rpr), head involution defective (hid), the apical caspase dronc, the Apaf-1ortholog dark, and the CD36 homolog croquemort (crq). In this study, I show that rpr and hid are 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. The competence to execute this hormone-triggered cell death command, however, is conferred through prior transcriptional down-regulation of the diap1 death repressor in mid-third instar larvae. I have found that salivary glands lacking the general transcriptional co-factor dCBP fail to repress diap1 transcription, resulting in persistent larval salivary glands despite the normal ecdysone-induction of death activators. dCBP is both necessary and sufficient to sensitize larval tissues for programmed cell death by down-regulating diap1 mRNA levels. I also show that 20-hydroxyecdysone can induce dCBP expression and that the ecdysone receptor is required for diap1 down-regulation in mid-third instar larval salivary glands. I propose that ecdysone-induced dCBP expression during larval development sensitizes the salivary glands for subsequent ecdysone-triggered cell death, providing competence to execute the death command. Collectively, these investigations demonstrate that ecdysone directs the programmed cell death of larval tissues during metamorphosis by disrupting the balance between death activator and death inhibitor levels through temporally distinct genetic programs.
Type Text
Publisher University of Utah
Subject Genetics; Physiology
Subject MESH Cell Death; Steroids; Drosophila
Dissertation Institution University of Utah
Dissertation Name PhD
Language eng
Relation is Version of Digital reproduction of "Genetic analysis of Drosophila steroid-triggered cell death." Spencer S. Eccles Health Sciences Library. Print version of "Genetic analysis of Drosophila steroid-triggered cell death." available at J. Willard Marriott Library Special Collection. QL3.5 2005 .Y55.
Rights Management © Viravuth Pho Yin.
Format application/pdf
Format Medium application/pdf
Format Extent 5,044,062 bytes
Identifier undthes,5447
Source Original: University of Utah Spencer S. Eccles Health Sciences Library (no longer available).
Master File Extent 5,044,095 bytes
ARK ark:/87278/s6gb25zp
Setname ir_etd
ID 191950
Reference URL https://collections.lib.utah.edu/ark:/87278/s6gb25zp
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