Mechanosensory Hair Cell Precursors in the Zebrafish Lateral Line

Hdl Handle:
http://hdl.handle.net/10675.2/345289
Title:
Mechanosensory Hair Cell Precursors in the Zebrafish Lateral Line
Authors:
Floyd, Tiffany L.
Abstract:
The vertebrate inner ear mediates the senses of hearing and balance. Contained within both the auditory and vestibular compartments of the inner ear are specialized mechanosensory hair cells that function as receptors and transducers of environmental stimuli. In all vertebrates, these sensory hair cells are particularly susceptible to ototoxic insults resulting in cell death and, in mammals, the irreversible loss of hair cells underlies deafness and balance disorders. In contrast to mammals, several non-mammalian vertebrates (including zebrafish) possess the innate capacity to produce new hair cells throughout life as well as regenerate hair cells that have been lethally damaged. A long-term strategy of the hearing research field is to determine the molecular mechanisms of hair cell regeneration using regenerating model systems such as zebrafish, then to apply this information to mammalian models where sensory hair cell regeneration is limited or nonexistent. During embryogenesis, sensory hair cell fates are specified through a mechanism of Notch-Delta-mediated lateral inhibition. The gamma secretase complex is an upstream regulator of Notch signaling, responsible for proteolytic\ cleavage and activation of the Notch receptor. Recent evidence suggests that Notch signaling may also play a role during the process of hair cell regeneration in zebrafish (Ma et al., 2008). I used a chemical inhibitor of the gamma secretase complex to examine the role of Notch signaling in the regulation of hair cell number maintenance in larval zebrafish. Results presented in this thesis provide novel insight into the mechanisms regulating the maintenance of resident hair cell precursors within the sensory epithelium. Moreover, this new information is directly relevant to research efforts in mammalian models by providing the molecular framework for therapeutic strategies designed to replace or regenerate lethally damaged hair cells in the mammalian cochlea by reactivating resident precursors to differentiate into hair cells.
Affiliation:
Institute of Molecular Medicine and Genetics
Issue Date:
Jul-2009
URI:
http://hdl.handle.net/10675.2/345289
Additional Links:
http://ezproxy.augusta.edu/login?url=http://search.proquest.com/docview/305058051?accountid=12365
Type:
Dissertation
Appears in Collections:
Theses and Dissertations

Full metadata record

DC FieldValue Language
dc.contributor.authorFloyd, Tiffany L.en
dc.date.accessioned2015-02-25T04:44:53Z-
dc.date.available2015-02-25T04:44:53Z-
dc.date.issued2009-07-
dc.identifier.urihttp://hdl.handle.net/10675.2/345289-
dc.description.abstractThe vertebrate inner ear mediates the senses of hearing and balance. Contained within both the auditory and vestibular compartments of the inner ear are specialized mechanosensory hair cells that function as receptors and transducers of environmental stimuli. In all vertebrates, these sensory hair cells are particularly susceptible to ototoxic insults resulting in cell death and, in mammals, the irreversible loss of hair cells underlies deafness and balance disorders. In contrast to mammals, several non-mammalian vertebrates (including zebrafish) possess the innate capacity to produce new hair cells throughout life as well as regenerate hair cells that have been lethally damaged. A long-term strategy of the hearing research field is to determine the molecular mechanisms of hair cell regeneration using regenerating model systems such as zebrafish, then to apply this information to mammalian models where sensory hair cell regeneration is limited or nonexistent. During embryogenesis, sensory hair cell fates are specified through a mechanism of Notch-Delta-mediated lateral inhibition. The gamma secretase complex is an upstream regulator of Notch signaling, responsible for proteolytic\ cleavage and activation of the Notch receptor. Recent evidence suggests that Notch signaling may also play a role during the process of hair cell regeneration in zebrafish (Ma et al., 2008). I used a chemical inhibitor of the gamma secretase complex to examine the role of Notch signaling in the regulation of hair cell number maintenance in larval zebrafish. Results presented in this thesis provide novel insight into the mechanisms regulating the maintenance of resident hair cell precursors within the sensory epithelium. Moreover, this new information is directly relevant to research efforts in mammalian models by providing the molecular framework for therapeutic strategies designed to replace or regenerate lethally damaged hair cells in the mammalian cochlea by reactivating resident precursors to differentiate into hair cells.en
dc.relation.urlhttp://ezproxy.augusta.edu/login?url=http://search.proquest.com/docview/305058051?accountid=12365en
dc.rightsCopyright protected. Unauthorized reproduction or use beyond the exceptions granted by the Fair Use clause of U.S. Copyright law may violate federal law.en
dc.subjectgamma secretase complexen
dc.subjectinner earen
dc.subjectMechanosensory hair cellsen
dc.subjecthair cellsen
dc.titleMechanosensory Hair Cell Precursors in the Zebrafish Lateral Lineen
dc.typeDissertationen
dc.contributor.departmentInstitute of Molecular Medicine and Geneticsen
dc.description.advisorKozlowski, Daviden
dc.description.committeeBollag, Wendy; Cameron, Richard; LeMosy, Ellen; McCluskey, Lynnette; Hamrick, Mark; Mumm, Jeffreyen
dc.description.degreeDoctor of Philosophy (Ph.D.)en
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