Fibroblast growth factor signalling regulates guidance gene expression

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dc.contributor.advisorMcFarlane, Sarah
dc.contributor.authorYang, Jung-Lynn Jonathan
dc.contributor.committeememberNguyen, Minh Dang
dc.contributor.committeememberSchuurmans, Carol
dc.contributor.committeememberBech-Hansen, Nils Torben
dc.contributor.committeememberChow, Robert
dc.date2018-02-16
dc.date.accessioned2018-01-25T19:03:37Z
dc.date.available2018-01-25T19:03:37Z
dc.date.issued2018-01-15
dc.description.abstractNeurons need to be properly connected to form a functioning neural network. Guidance cues expressed in the neuron’s surroundings help locate postsynaptic targets and also mediate cell migration and morphology. The expression of guidance cues must be tightly controlled to precisely orchestrate the process of wiring the nervous system. These guidance cues and their receptors have been identified, but the mechanisms that control the expression of guidance genes, especially the genes for guidance cues, are relatively unknown. In particular, Slit1 and Sema3a are expressed in the forebrain of the African clawed frog, Xenopus laevis, to direct the growth of the optic tract toward the visual target in the brain, the optic tectum. Fibroblast growth factor (Fgf) signalling maintains the expression of slit1 and sema3a during optic tract development. I demonstrate how Fgf receptors (Fgfrs) regulate the slit1 and sema3a promoters and characterize the −2285+326slit1 and −2930+63sema3a sequences to locate silencers and core promoters. In the forebrain, Fgfr1 modulates slit1 expression, and Fgfr2-4 regulate sema3a expression. Then, I explore signalling pathways downstream of Fgfr activation that modify slit1 and sema3a expression. PI3K-Akt signalling promotes slit1 and sema3a expression, but active MAPK signalling is sufficient to downregulate these guidance genes. Further, because Fgf signalling controls the expression of Lhx2/9 and Etv1, I choose these as candidate transcription factors for slit1 and sema3a expression. In vitro and in vivo, Lhx2 and Etv1 repress and transactivate, respectively, slit1 and sema3a. In vitro, Lhx9 gain of function downregulates slit1. The focus of this thesis is guidance cue regulation, specifically, the mechanisms of how Fgf signalling regulates slit1 and sema3a expression through Fgfrs, intracellular signalling pathways, and transcription factors, thereby connecting extrinsinc factors to intrinsic control of guidance cue expression.en_US
dc.identifier.citationYang, J. L. J. (2018). Fibroblast growth factor signalling regulates guidance gene expression (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/5411
dc.identifier.urihttp://hdl.handle.net/1880/106330
dc.language.isoenen_US
dc.publisher.facultyCumming School of Medicineen_US
dc.publisher.institutionUniversity of Calgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.en_US
dc.subject.classificationEducation--Healthen_US
dc.subject.classificationEducation--Sciencesen_US
dc.subject.classificationAnatomyen_US
dc.subject.classificationBioinformaticsen_US
dc.subject.classificationBiology--Cellen_US
dc.subject.classificationGeneticsen_US
dc.subject.classificationBiology--Molecularen_US
dc.subject.classificationNeuroscienceen_US
dc.titleFibroblast growth factor signalling regulates guidance gene expressionen_US
dc.typedoctoral thesisen_US
thesis.degree.disciplineMedicine – Neuroscienceen_US
thesis.degree.grantorUniversity of Calgaryen_US
thesis.degree.nameDoctor of Philosophy (PhD)en_US
ucalgary.item.requestcopytrue
ucalgary.thesis.checklistI confirm that I have submitted all of the required forms to Faculty of Graduate Studies.en_US
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