Genetic Screen and Functional Analysis of Steroid-Triggered Cell Death in Drosophila

Update item information
Publication Type dissertation
School or College School of Medicine
Department Human Genetics
Author Wang, Lei
Title Genetic Screen and Functional Analysis of Steroid-Triggered Cell Death in Drosophila
Date 2010-02-22
Description The steroid hormone ecdysone triggers the stage-specific destruction of Drosophila larval tissues through transcriptional cascades that induce two distinct forms of programmed cell death: caspase-dependent apoptosis and lysosome-mediated autophagy. In this thesis, I describe the use of genetic screens to further our understanding of the steroid-triggered programmed cell death response. Pupal lethal mutants were screened for specific defects in the destruction of larval salivary glands. A pilot screen using existing collections of P-element insertions resulted in the identification of known cell death regulators as well as mutations in novel regulators of cell death, such as dCBP and dTrf2. A large-scale EMS mutagenesis screen on the third chromosome identified 48 mutants, which include seven multiallelic complementation groups. At least five of these groups represent novel regulators of cell death, three of which were mapped to specific genes: CG5146, Med24, and CG7998.1 further characterized two of these genes, Med24 and CG7998, for their roles in salivary gland cell death. I showed that mutations in CG7998 and Med24 selectively block caspase activation without affecting autophagy in persistent mutant salivary glands. CG7998 encodes a malate dehydrogenase that localizes to the mitochondria. Although mitochondrial number and morphology appear normal in CG7998 mutant salivary glands, these animals have significantly lower levels of ATP and accumulate late-stage citric acid cycle intermediates, suggesting that the cell death defects arise from a deficit in cellular energy production. Med24 encodes a component of the Mediator transcriptional coactivator complex. Unexpectedly, however, the ecdysone-induction of key death regulator genes occurs normally in Med.24 mutant salivary glands. This study identifies novel mechanisms for regulating the destruction of larval tissues during Drosophila metamorphosis, and provides new directions for defining the molecular mechanisms of steroid-triggered programmed cell death during development.
Type Text
Publisher University of Utah
Subject Drosophila; Cell Death; Steroids
Subject MESH Steroids; Drosophila; Cell Death
Dissertation Institution University of Utah
Dissertation Name PhD
Language eng
Relation is Version of Digital reproduction of "Genetic screen and functional analysis of steroid-triggered cell death in drosophila." Print version of "Genetic screen and functional analysis of steroid-triggered cell death in drosophila." available at J.Willard Marriott Library Speical Collection. QL3.5 2009.W36
Rights Management © Lei Wang
Format Medium application/pdf
Format Extent 1,447,122 bytes
Source Original: University of Utah Spencer S. Eccles Health Sciences Library
Conversion Specifications Original scanned on Fujitsu fi-5220G as 400 dpi to pdf using ABBYY FineReader 10
ARK ark:/87278/s6hd894v
Setname ir_etd
Date Created 2012-04-23
Date Modified 2021-05-06
ID 192197
Reference URL https://collections.lib.utah.edu/ark:/87278/s6hd894v
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