Toll-7 and Toll-6: central nervous system functions as Drosophila neurotrophin receptors

3098 19 31456 5 67777 document 31456 McIlroy12PhD.pdf application/pdf 36a8eba64ea9e6f0b35c8a208ccacf7c MD5 6370082 2013-09-17 11:40:31 http://etheses.bham.ac.uk//id/eprint/3098/1/McIlroy12PhD.pdf 3098 1 1 application/pdf application/pdf en public

McIlroy12PhD.pdf

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http://eprints.org/relation/isVersionOf http://etheses.bham.ac.uk/id/document/31456 http://eprints.org/relation/isVolatileVersionOf http://etheses.bham.ac.uk/id/document/31456 http://eprints.org/relation/isIndexCodesVersionOf http://etheses.bham.ac.uk/id/document/31456 archive 4031 disk0/00/00/30/98 2012-09-21 10:47:57 2019-01-23 09:55:32 2012-09-21 10:47:57 thesis show 0 McIlroy Graham William Hidalgo Alicia University of Birmingham Toll-7 and Toll-6: central nervous system functions as Drosophila neurotrophin receptors unpub QH301 QR180 RC0321 10col_life Was originally embargoed, but author requested to lift embargo and make the thesis openly accessible, August 2013. The Drosophila Toll receptor is crucial for dorsoventral patterning in embryos, and for innate immunity. Toll also functions during central nervous system development, promoting neuronal survival and targeting. There are nine Toll paralogues in Drosophila, and it is unknown whether any of these also function in the CNS. Toll’s ligand, Spz, has an NGF domain. NGF is a vertebrate neurotrophin - a growth factor that regulates the development and function of the nervous system. Drosophila Neurotrophin 1 (DNT1), identified by homology to the vertebrate neurotrophin BDNF, and DNT2 are paralogues of spz. The three DNTs – DNT1, DNT2 and spz – are structural and functional homologues of vertebrate neurotrophins, and they promote neuronal survival, targeting and synaptogenesis in Drosophila. However, the receptors for DNT1 and DNT2 are unknown. Here, using a combination of in situ hybridisations and reporters that drive GFP expression, I investigate the expression of Toll paralogues in the Drosophila nervous system. By generating null mutant flies and gain-of-function transgenic flies, I examine genetic interactions between Tolls and DNTs. I also investigate the rolls of these receptors in adult locomotion, axon targeting and cell survival. Finally, in cell culture, I test whether DNTs can signal through Tolls to activate NFκB. 2012-07 2011-09 graduation eng author unchecked This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder. public 297 University of Birmingham School of Biosciences d_ph mrc 2012-07 graduation