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dc.contributor.advisorY. Tony Ip
dc.contributor.authorChatterjee, Madhurima
dc.date2022-08-11T08:08:43.000
dc.date.accessioned2022-08-23T16:05:47Z
dc.date.available2022-08-23T16:05:47Z
dc.date.issued2011-12-21
dc.date.submitted2012-06-14
dc.identifier.doi10.13028/0h78-6g93
dc.identifier.urihttp://hdl.handle.net/20.500.14038/31942
dc.description.abstractTissue homeostasis in the adult Drosophila melanogaster intestine is maintained by controlling the proper balance of stem cell self-renewal and differentiation. In the adult fly midgut, intestinal stem cells (ISCs) are the only dividing cells and their identity maintenance is crucial to the proper functioning of the fly gut. Various pathways such as Notch, JAK-STAT and Wingless are known to regulate ISC division and differentiation. Here I used a pathogen feeding model to study conditions that accelerate ISC division and guide intestinal cell differentiation favoring enterocyte development. I also examined the role of Tumor Suppressor Gene 101 (TSG101) in ISC maintenance and function. TSG101, a part of the ESCRT1 complex. It is known to stimulate the Notch pathway and to play a role in endocytic trafficking. TSG101 loss-of-function mutants show developmental defects in various fly and mammalian tissues. The protein also plays a role in virus abscission from host cells. In my experiments I have observed that TSG101 is required for ISC maintenance. TSG101 knockdown and loss of function mutant clones have defects in ISC proliferation that hinder the normal intestinal responses to oral pathogen ingestion. Based on these results I conclude that TSG101 is needed in the adult fly intestine for proper ISC maintenance and function, thereby being an important player in intestinal homeostasis.
dc.language.isoen_US
dc.rightsCopyright is held by the author, with all rights reserved.
dc.subjectGenes
dc.subjectTumor Suppressor
dc.subjectDNA-Binding Proteins
dc.subjectTranscription Factors
dc.subjectEndosomal Sorting Complexes Required for Transport
dc.subjectHomeostasis
dc.subjectIntestines
dc.subjectDrosophila melanogaster
dc.subjectAmino Acids, Peptides, and Proteins
dc.subjectAnimal Experimentation and Research
dc.subjectCell and Developmental Biology
dc.subjectDigestive System
dc.subjectGenetic Phenomena
dc.subjectNeoplasms
dc.subjectPhysiology
dc.titleIntestine Homeostasis and the Role of Tumor Suppressor Gene 101 in Drosophila Melanogaster: A Dissertation
dc.typeDoctoral Dissertation
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1599&context=gsbs_diss&unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_diss/597
dc.legacy.embargo2013-04-20T00:00:00-07:00
dc.identifier.contextkey2992551
refterms.dateFOA2022-08-30T15:25:17Z
html.description.abstract<p>Tissue homeostasis in the adult <em>Drosophila melanogaster</em> intestine is maintained by controlling the proper balance of stem cell self-renewal and differentiation. In the adult fly midgut, intestinal stem cells (ISCs) are the only dividing cells and their identity maintenance is crucial to the proper functioning of the fly gut. Various pathways such as Notch, JAK-STAT and Wingless are known to regulate ISC division and differentiation.</p> <p>Here I used a pathogen feeding model to study conditions that accelerate ISC division and guide intestinal cell differentiation favoring enterocyte development. I also examined the role of Tumor Suppressor Gene 101 (TSG101) in ISC maintenance and function. TSG101, a part of the ESCRT1 complex. It is known to stimulate the Notch pathway and to play a role in endocytic trafficking. TSG101 loss-of-function mutants show developmental defects in various fly and mammalian tissues. The protein also plays a role in virus abscission from host cells. In my experiments I have observed that TSG101 is required for ISC maintenance. TSG101 knockdown and loss of function mutant clones have defects in ISC proliferation that hinder the normal intestinal responses to oral pathogen ingestion.</p> <p>Based on these results I conclude that TSG101 is needed in the adult fly intestine for proper ISC maintenance and function, thereby being an important player in intestinal homeostasis.</p>
dc.identifier.submissionpathgsbs_diss/597
dc.contributor.departmentProgram in Molecular Medicine
dc.description.thesisprogramInterdisciplinary Graduate Program


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