|Title:||The carboxyl-terminal binding protein-1 (CTBP-1) can function in the nervous system to regulate longevity, gene expression and axon guidance|
|Publisher:||University of Sydney.|
Faculty of Science.
School of Molecular Bioscience.
|Abstract:||C-terminal binding proteins (CtBPs) are recruited by a variety of transcription factors to mediate gene repression. C. elegans CTBP-1 has previously been shown to play a role in the regulation of lifespan; Caenorhabditis elegans strains carrying a deletion in the ctbp-1 gene showed a 10-20% increase in mean and maximal lifespan compared with wild-type control strains. We set out to identify the tissues in which CTBP-1 functions to regulate lifespan in C. elegans. Our analysis of reporter genes shows that CTBP-1 is predominantly expressed in the nervous system with lower levels detectable in the hypodermis. Tissue-specific rescue experiments demonstrated that CTBP-1 functions in the nervous system to regulate lifespan. Previously, the lifespan extension in a ctbp-1 mutant was attributed, at least in part, to the misregulation of a lipase gene, lips-7. We found that expressing CTBP-1 solely in the nervous system of a ctbp-1 mutant significantly reduced lips-7 transcription. Locomotory behaviours such as exploration behaviour are regulated by a neuronal circuit involving many subtypes of neurons and incorrect development or function of these neurons results in changes in these behaviours. We observed reduced exploration behaviour in ctbp-1 mutants. Our examination of a subset of neurons involved in regulating locomotion, among which are the dorsal SMD (SMDD) neurons, revealed that SMDD axons are misguided in ctbp-1 mutants. Expressing CTBP-1 under the control of the endogenous ctbp-1 promoter rescued the SMDD axon guidance defect in ctbp-1 mutants. Additional rescue experiments suggest that CTBP-1 functions in the nervous system to regulate SMDD axon guidance. Interestingly, the pre-synaptic marker RAB-3 was found to localise to the misguided portion of SMDD axons in a ctbp-1 mutant. In summary, our findings show that CTBP-1 can function in the nervous system to regulate longevity, gene expression and axon guidance.|
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|Rights and Permissions:||The author retains copyright of this thesis. It may only be used for the purposes of research and study. It must not be used for any other purposes and may not be transmitted or shared with others without prior permission.|
|Type of Work:||PhD Doctorate|
|Type of Publication:||Doctor of Philosophy Ph.D.|
|Appears in Collections:||Sydney Digital Theses (University of Sydney Access only)|
|2015_Anna_Reid_Thesis.pdf||PhD Thesis||7.81 MB||Adobe PDF|