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dc.contributor.advisorBeck, Caroline
dc.contributor.advisorMercer, Alison
dc.contributor.authorTaylor, Amy Janet
dc.date.available2013-09-29T20:29:43Z
dc.date.copyright2013
dc.identifier.citationTaylor, A. J. (2013). The Role of Epigenetics in Amphibian Regeneration (Thesis, Doctor of Philosophy). University of Otago. Retrieved from http://hdl.handle.net/10523/4306en
dc.identifier.urihttp://hdl.handle.net/10523/4306
dc.description.abstractUp until recently, epigenetic mechanisms for epimorphic regeneration have not been studied. Epigenetic mechanisms present a possible method for control over the regeneration process and an explanation as to why some animals possess regenerative abilities and others do not. This thesis provides evidence for a role for histone acetylation and DNA methylation in amphibian regeneration. Results from this thesis show that histone deacetylase (HDAC) enzymes and consequently histone hypoacetylation are needed for successful regeneration with X. laevis tadpoles, treated with HDAC inhibitors, failing to regenerate tails and limbs. HDACs are also shown to be necessary for A. mexicanum tail regeneration however HDAC inhibition only slows limb regeneration in A. mexicanum. HDAC inhibition is shown not to affect limb or tail development in X. laevis but to slow development in A. mexicanum. Direct measurement of HDAC activity in X. laevis is consistent with the results of HDAC inhibitor treatment, with increased HDAC activity being associated with regeneration success in X. laevis. Regeneration competent tadpoles show increased HDAC activity with amputation and regeneration incompetent refractory stage tadpoles show a decrease in HDAC activity with amputation. HDAC activity is possibly associated with the BMP and Notch signalling pathways as well as retinoic acid signalling. Global DNA methylation is also measured in X. laevis. Low levels of DNA methylation are shown to be associated with regeneration success following amputation, with regeneration competent tadpoles showing lower levels of methylation than refractory stage tadpoles. This is consistent with the illustrated variable regenerative response to methyltransferase inhibitor treatment in regeneration competent tadpoles treated after amputation. It is also consistent with the increased regenerative success seen when refractory stage tadpoles are treated with a methyltransferase inhibitor. The evidence presented in this thesis illustrates the importance of epigenetic mechanisms in vertebrate regeneration. This research may have important implications for medical research.
dc.language.isoen
dc.publisherUniversity of Otago
dc.rightsAll items in OUR Archive are provided for private study and research purposes and are protected by copyright with all rights reserved unless otherwise indicated.
dc.subjectRegeneration
dc.subjectXenopus laevis
dc.subjectAmbystoma mexicanum
dc.subjectepimorphic
dc.subjectepigenetics
dc.subjectHDAC
dc.subjectmethylation
dc.subjectlimb
dc.subjecttail
dc.titleThe Role of Epigenetics in Amphibian Regeneration
dc.typeThesis
dc.date.updated2013-09-28T22:49:25Z
dc.language.rfc3066en
thesis.degree.disciplineZoology
thesis.degree.nameDoctor of Philosophy
thesis.degree.grantorUniversity of Otago
thesis.degree.levelDoctoral
otago.interloanno
otago.openaccessAbstract Only
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