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dc.contributor.authorCelestrin, Kevin
dc.date.accessioned2018-07-12T17:02:01Z
dc.date.available2018-07-12T17:02:01Z
dc.date.issued2018
dc.identifier.citationSource: Dissertation Abstracts International, Volume: 79-09(E), Section: B.;Advisors: Hannes Bulow.
dc.identifier.urihttp://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqm&rft_dat=xri:pqdiss:10834829
dc.identifier.urihttps://hdl.handle.net/20.500.12202/502
dc.description.abstractDendrites are important in the central nervous system, where it has been shown that individuals with neuropsychiatric disorders, such as Schizophrenia and Alzheimer's show defects in dendrite morphology. In the peripheral nervous system dendrites are important for receiving various modalities of external stimuli from the environment. For my thesis work I used Caenorhabditis elegans, and its complex mechanosensory neuron PVD to study the genetic mechanisms required for dendrite morphogenesis. Previous studies have shown a few non-cell autonomous molecules are required for PVD dendrite morphology. I performed candidate screens to determine if there are any other non-cell autonomous cues required for the formation of PVD dendritic branches. In this work I will discuss the candidate screening of the heparan sulfate proteoglycans, which revealed that the secreted basement membrane molecule unc-52 /periecan is required for the formation of PVD dendritic branches. Since unc-52/periecan is part of the muscle-skin attachment site complex, I screened the muscle-skin attachment site complex genes and found that several of these genes are required for PVD dendritic branch formation. Several of the attachment complex genes show a reduction in the number of secondary branches in PVD. The secreted ECM protein unc-52/perlecan showed the most severe reduction in PVD secondary branches. In this work I characterize the PVD phenotypes in the unc-52/perlecan mutants and found that several of them show a similar reduction in secondary branch number. I further characterized PVD in unc-52/perlecan mutants by analyzing the left-right bias found between PVDL and PVDR. I found that this left-right bias is maintained in unc-52/periecan mutants. I analyzed the dorsal-ventral bias in PVD neurons in an unc-52 mutant background and found that this bias is maintained in the unc-52 /periecan mutants. Through the use of a deficiency that deletes the region of chromosome II that contains unc-52/periecan I have shown that unc-52 mutants are genetic nulls for the PVD secondary branch defects. An unc-52/perlecan mutation (ra515 ), which deletes four immunoglobulin domains, shows PVD secondary branch defects, but no locomotion defects unlike the other unc-52 mutants. I performed analysis of the body wall muscle in the unc-52 ra515 to determine that the defects I observe in PVD secondary dendritic branches in the unc-52/perlecan mutant backgrounds are due to loss of unc-52 and not a secondary phenotype of defects in the body wall muscle. Through genetic and biochemical analysis I found that unc-52/perlecan genetically and physically interacts with the ECM protein nid-1/nidogen, which also shows a reduction in PVD secondary branches. Utilizing genetic analysis I found that unc-52/perelcan also genetically interacts with the netrin pathway, which has been shown to regulate the morphology of secondary and tertiary dendritic branches.
dc.publisherProQuest Dissertations & Theses
dc.subjectGenetics.
dc.subjectBiology.
dc.subjectNeurosciences.
dc.titleThe role of unc-52/perlecan in PVD dendritic branch formation
dc.typeDissertation


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