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dc.contributor.advisorGross, Jeffrey Martinen
dc.creatorBibliowicz, Jonathanen
dc.date.accessioned2011-09-22T16:17:45Zen
dc.date.available2011-09-22T16:17:45Zen
dc.date.issued2011-08en
dc.date.submittedAugust 2011en
dc.identifier.urihttp://hdl.handle.net/2152/ETD-UT-2011-08-4184en
dc.descriptiontexten
dc.description.abstractThe Hedgehog receptor Patched (Ptch) is a well-studied tumor suppressor. Mutations in Ptch have been linked to mis-regulation of stem cell proliferation and tumorigenesis in numerous contexts. To study the role of Ptch function during retinal development and homeostasis, I analyzed retinal growth and patterning in the embryonic and post-embryonic (juvenile) zebrafish ptc2 mutant line. ptc2 deficiency in zebrafish results in an expansion of the stem/progenitor population of the ciliary marginal zone (CMZ), as well as ectopic proliferation within the neural retina at juvenile stages. ptc2-/- mutants also possess vitreo-retinal abnormalities that appear to be embryonic in origin. These phenotypes are similar to the ocular abnormalities previously reported in human patients suffering from Basal Cell Naevus Syndrome (BCNS), a disorder that has been linked to mutations in the human PTCH gene (the orthologue of the zebrafish ptc2), and point to the utility of the ptc2 mutant line as a model for the study of BCNS-related ocular pathologies. In addition, peripheral retinal dysplasias that include ectopic neuronal clusters and disrupted lamination were observed at later, juvenile stages. It has been previously proposed that retinal over-proliferation might contribute to retinal dysplasias observed in the post-natal Ptch1 /- mice (an established model for BCNS); however, this potential relationship has yet to be established experimentally. I demonstrated that a population of ectopically proliferating cells give rise to the ectopic neuronal clusters in the INL of ptc2-/- mutants and established ectopic proliferation as the likely cellular underpinning of retinal dysplasia in juvenile ptc2-/- mutants.en
dc.format.mimetypeapplication/pdfen
dc.language.isoengen
dc.subjectRetinaen
dc.subjectHedgehogen
dc.subjectDiseaseen
dc.subjectZebrafishen
dc.subjectPatcheden
dc.titleThe hedgehog pathway in retinal development and diseaseen
dc.date.updated2011-09-22T16:18:50Zen
dc.identifier.slug2152/ETD-UT-2011-08-4184en
dc.contributor.committeeMemberFISCHER, JANICE A.en
dc.contributor.committeeMemberMORGAN, JENNIFERen
dc.contributor.committeeMemberTHOMPSON, WESLEYen
dc.contributor.committeeMemberVOKES, STEVEN A.en
dc.description.departmentCellular and Molecular Biologyen
dc.type.genrethesisen
thesis.degree.departmentCellular and Molecular Biologyen
thesis.degree.disciplineCell and Molecular Biologyen
thesis.degree.grantorUniversity of Texas at Austinen
thesis.degree.levelDoctoralen
thesis.degree.nameDoctor of Philosophyen


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