Genetic regulation of autophagic cell death in Drosophila Melanogester

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dc.contributor.advisorBaehrecke, Eric Hen_US
dc.contributor.authorDutta, Sudeshnaen_US
dc.contributor.departmentMolecular and Cell Biologyen_US
dc.contributor.publisherDigital Repository at the University of Marylanden_US
dc.contributor.publisherUniversity of Maryland (College Park, Md.)en_US
dc.date.accessioned2009-01-24T07:23:43Z
dc.date.available2009-01-24T07:23:43Z
dc.date.issued2008-11-20en_US
dc.description.abstractApoptosis and autophagic cell death are the two most prominent morphological forms of programmed cell death that occur during animal development. While much is known about the mechanisms that regulate apoptosis, relatively little is known about autophagic cell death. The steroid hormone ecdysone coordinates multiple cellular processes during metamorphosis in Drosophila, including cell differentiation, morphogenesis and death. E93 is necessary and sufficient for larval tissue cell death during metamorphosis, including autophagic cell death of salivary glands. Here we characterize new mutant alleles of a dominant wing vein mutation Vein-off (Vno), and provide evidence that E93 and Vno are related. Our data also indicate that E93 functions in steroid regulation of both cell development and death during metamorphosis. E93 encodes a helix-turn-helix DNA binding motif and binds to specific regions of salivary gland polytene chromosomes. We have used genetic and genomic approaches to identify downstream targets of E93. We have identified numerous candidate E93 target genes using DNA microarrays, and have generated transgenic animals to identify downstream target genes of E93 by chromatin immune precipitation. We show that one putative E93 target gene, hippo (hpo), is required for salivary gland cell death. The Wts/Hpo tumor-suppressor pathway is a critical regulator of tissue growth in animals, but it is not clear how this signaling pathway controls cell growth. Our data indicate that salivary gland degradation requires genes in the Wts/Hpo pathway. Wts is required for cell growth arrest and autophagy in dying salivary glands, and regulates the degradation of this tissue in a PI3K-dependent manner.en_US
dc.format.extent2854363 bytes
dc.format.mimetypeapplication/pdf
dc.identifier.urihttp://hdl.handle.net/1903/8860
dc.language.isoen_US
dc.subject.pqcontrolledBiology, Molecularen_US
dc.subject.pqcontrolledBiology, Cellen_US
dc.subject.pqcontrolledBiology, Geneticsen_US
dc.subject.pquncontrolledcell deathen_US
dc.subject.pquncontrolledDrosophila geneticsen_US
dc.subject.pquncontrolledAutophagyen_US
dc.subject.pquncontrolledPI3K pathwayen_US
dc.subject.pquncontrolledE93en_US
dc.subject.pquncontrolledwtsen_US
dc.titleGenetic regulation of autophagic cell death in Drosophila Melanogesteren_US
dc.typeDissertationen_US

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