Investigating the role of Capicua in mediating FGF transcriptional regulation in X. tropicalis

Abstract

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.

Metadata

Supervisors:	Isaacs, Harry Victor
Awarding institution:	University of York
Academic Units:	The University of York > Biology (York)
Depositing User:	Mr Michael Gavin King
Date Deposited:	04 Jun 2019 13:39
Last Modified:	04 Jun 2019 13:39

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Filename: Michael King Thesis 24-05-19.pdf

Description: PhD Thesis

Supplementary Material

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Filename: CIC-LH~1.GB

Description: CIC-L human mouse alignment

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Filename: CIC-LH~1.PDF

Description: CIC-L human mouse alignment pdf

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Filename: CIC-SH~1.GB

Description: CIC-S human mouse alignment

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Filename: CIC-SH~1.PDF

Description: CIC-S human mouse alignment pdf

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Filename: CIC alignments without exon 21.bmp

Description: CIC alignments without exon 21

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Filename: pCS2+ X. tropicalis CIC-S Map.png

Description: pCS2+ X. tropicalis CIC-S Map

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Filename: pCS2+ X. tropicalis CIC-S.dna

Description: pCS2+ X. tropicalis CIC-S Map

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Filename: Xenopus_tropicalis.capicua_annotation.2018-09-27.xlsx

Description: Xenopus_tropicalis.capicua_annotation.2018-09-27 RNAseq

Supplementary Material

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Filename: 1CIC-L~1.MPG

Description: 1. CIC-L targeting morpholino injections.

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Filename: 2CIC-S~1.MPG

Description: 2. CIC-S targeting morpholino injections.

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Filename: 3CIC-L~1.MPG

Description: 3. CIC-L & CIC-S targeting morpholino injections.

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Filename: 4UNINJ~1.MPG

Description: 4. Uninjected control.

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Filename: X. trop CIC-L cDNA.dna

Description: X. trop cDNA sequence CIC-L

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Filename: X. trop CIC-S cDNA.dna

Description: X. trop cDNA sequence CIC-S

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Filename: snapgene_viewer_4.2.11_win.exe

Description: SnapGene Softwre

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 2.5 License

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Supplementary Material

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Filename: X. trop CIC gene Map.dna

Description: X. trop CIC gene Map

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