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dc.contributor.advisorJurisch-Yaksi, Nathalie
dc.contributor.authorReiten, Ingrid
dc.date.accessioned2017-04-07T11:29:44Z
dc.date.available2017-04-07T11:29:44Z
dc.date.issued2016
dc.identifier.urihttp://hdl.handle.net/11250/2437149
dc.description.abstractThe structure of all cilia is remarkably well conserved from single-celled organisms to mammals, and they have well-established roles as motile and sensory organelles in various species. The propulsive motility of beating cilia serves high-impact biological functions in the tissues where they are located. Mutations in ciliary genes, which impair the function and presence of motile cilia, can lead to various human pathologies, known as ciliopathies. Significant advances have been made the last twenty years in understanding the importance of cilia, but much is yet unknown about the physiological role these organelles play in most tissues. Thus, more research addressing ciliary biology and function is needed to eventually bring about better ways to cure or treat people whose lives are impacted by defective cilia. Zebrafish is a unique model organism to study the role of cilia in human diseases and vertebrate development, due to their high amenability to genetic engineering techniques and the genetic and developmental similarities between humans and zebrafish. They develop multiciliated cells (MCCs) and olfactory receptor neurons (ORNs) in the olfactory pit early in embryogenesis, establishing the zebrafish olfactory epithelium as an easily accessible ciliated organ for high-throughput studies of ciliary characteristics. In the first part of my work, I characterized cilia morphology and physiology by investigating ciliary beating in the olfactory epithelium of zebrafish larvae and discussing potential regulatory mechanisms. To do this, we developed and automated a method that allows analysis of ciliary beating frequency (CBF) from high-speed video recordings. Various stimuli were tested for a potential effect on the CBF. The frequency of beating increased upon shear force induced by water flow and upon exposure to higher temperatures (up to 32°C). Larvae were also treated with different chemicals, namely denatonium (20mM), KCl (40mM) and forskolin (25μM), but CBF was not affected in either of the treatments. Neither an optogenetic activation of ORNs modified ciliary beating. Furthermore, my findings suggest that calcium (Ca2+) is not involved in regulating the CBF of motile cilia in the olfactory pit, as opposed to what has been shown for many other MCCs. Genetic mutants with ablated or defective cilia are suited to investigate the function of motile cilia in the olfactory pit of zebrafish larvae. I characterized 5 mutant lines, with emphasis on the distribution of cilia in the olfactory pit and their beating properties, to provide new tools for future ciliary research. The zebrafish schmalhans (smh) mutant have IV a mutation in ccdc103, which only affect motility and no other aspects of cilia, and is therefore suitable for investigation of early developmental effects solely induced by ciliary beating. Potentially, this mutant will ultimately allow us to understand the function of motile cilia in the olfactory pit and identify whether they are important for olfactory responses. By the characterization of mutant lines and adequate methods to detect ciliary beating and other ciliary properties, we hope this work will lead forth to an establishment of zebrafish genetic mutants as a toolkit for identification of molecules and pathways curing ciliopathies.nb_NO
dc.language.isoengnb_NO
dc.publisherNTNUnb_NO
dc.subjectNeurosciencenb_NO
dc.titleThe sensory role of motile cilianb_NO
dc.typeMaster thesisnb_NO
dc.subject.nsiVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710nb_NO
dc.description.localcodeOppgaven er tilgjengelig fra 2021-06-13.


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