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Title: Investigating the role of Capicua in mediating FGF transcriptional regulation in X. tropicalis
Author: King, Michael Gavin
Awarding Body: University of York
Current Institution: University of York
Date of Award: 2018
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Full text unavailable from EThOS. Thesis embargoed until 24 May 2024
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The Fibroblast Growth Factor (FGF) family of secreted peptides signal through tyrosine kinase receptors (RTKs), leading to the downstream activation of the MAP kinase (MAPK), causing transcriptional change. FGF signalling plays multiple critical roles in the maintenance of mesoderm induction, regulation of differentiation and patterning throughout early embryonic development. Despite extensive research on the FGF dependent transcriptome, there are still gaps in are understanding of gene regulation downstream of FGF signalling. The aim of this project was to address the gaps in knowledge by investigating a novel regulator of transcription, Capicua (CIC). D. melanogaster research has revealed that CIC functions as a transcriptional repressor downstream of RTKs, EGFR and Torso, regulated by Ras-MAPK signal transduction. This project's focus was on establishing if CIC is involved as a transcriptional repressor downstream of FGF signalling, functioning in a similar fashion to EGFR and Torso gene transcription during early amphibian development. The work in this thesis has established the gene structure of CIC in X. tropicalis, allowing the analysis of temporal and spatial expression profiles of the prominent isoforms of CIC. Analysis has shown that CIC-L is expressed in the maternal phase of embryonic development, whilst CIC-S is zygotically expressed. Given the deep conservation of developmental mechanisms within vertebrate species and the increasing evidence linking both FGF signalling and the function of CIC in human health and disease, the output of this investigation will have a wide significance.
Supervisor: Isaacs, Harry Victor Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available