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dc.contributor.advisorBeisel, Kirk W.en_US
dc.contributor.authorPecka, Jason Leeen_US
dc.date.accessioned2013-05-14T15:27:09Z
dc.date.available2013-06-01T13:40:18Z
dc.date.issued2013-04en_US
dc.identifier.urihttp://hdl.handle.net/10504/42558
dc.description.abstractHearing loss due to injury of the sensory hair cells of the inner ear is largely irreversible in mammals. ATOH1, a proneural basic helix loop helix transcription factor is essential for inner ear hair cell differentiation and has garnered particular interest as a potential regeneration tool. Additionally, the transcription factors, POU4F3 and GFI1, are important in maturation and maintenance of inner ear hair cells and compel attention themselves. However, the roles of these transcription factors and their interrelationship in hair cell development and maintenance are not completely understood. In order to define a regulatory relationship between these transcription factors requires further study. We transfected a prosensory inner ear precursor cell line with these transcription factors and investigated the global transcriptome changes through microarray analysis and confirmed with quantitative RT-PCR. Furthermore, we employed a bioinformatic approach to explore the promoter regions of these genes and examined potential biological relationships through the Ingenuity Pathway Analysis software. We demonstrate that the regulatory pathways between Atoh1, Pou4f3 and Gfi1 are indirect and together comprise a larger gene regulatory network rather than a direct sequential cascade. Further evaluation revealed that these transcription factors differentially express genes classified into cell cycle and cell proliferation gene ontology categories. Pou4f3 displayed a potential to regulate multiple genes correlated with apoptosis, through which it may exhibit an important facilitatory function in hair cell maintenance. Finally, we illustrate for the first time the potential ability of Atoh1 and Gfi1 to regulate levels of certain proteins through differential regulation of the Ubc gene and cell cycle-associated binding partners.en_US
dc.language.isoen_USen_US
dc.publisherCreighton Universityen_US
dc.rightsCopyright is retained by the Author. A non-exclusive distribution right is granted to Creighton University and to ProQuest following the publishing model selected above.en_US
dc.subject.meshHair Cells, Auditory, Outer--physiologyen_US
dc.subject.meshMotor Activity--physiology.en_US
dc.titleStudying the Atoh1 Gene Regulatory Networken_US
dc.typeThesis
dc.rights.holderJason L. Peckaen_US
dc.publisher.locationOmaha, Nebraskaen_US
dc.description.noteProQuest Traditional Publishing Optionen_US
dc.description.pagesxii, 123 pagesen_US
dc.contributor.cuauthorPecka, Jason Leeen_US
dc.embargo.terms2013-06-01
dc.degree.levelMS (Master of Science)en_US
dc.degree.disciplineBiomedical Sciences (graduate program)en_US
dc.degree.nameM.S. in Biomedical Sciencesen_US
dc.degree.grantorGraduate Schoolen_US
dc.degree.committeeWeston, Michaelen_US
dc.degree.committeeHe, David Z. Z.en_US
dc.degree.committeeSoukup, Garrett A.en_US


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