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Title: An analysis of FGF-regulated genes during Xenopus neural development
Author: Brunsdon, Hannah
ISNI:       0000 0004 5369 2805
Awarding Body: University of York
Current Institution: University of York
Date of Award: 2015
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FGF signalling is pivotal in early vertebrate development and is involved in cell movements, germ layer induction and organogenesis. There is also evidence of an important role of FGF signalling in the specification and patterning of posterior neural tissues. Transcriptional targets of FGF signalling during germ layer specification have been identified recently by previous lab members. However, less is known about FGF targets active during neural development. The aim of this project was to investigate proximal downstream targets of FGF signalling in the context of early neural development by using drug-inducible forms of Xenopus FGF receptors, iFGFRs 1-4. The effect of iFGFR 1-4 induction in Xenopus laevis during gastrulation was initially investigated through analysis of a microarray dataset. This, and investigation of phenotypes of embryos expressing iFGFRs, found that each iFGFR had distinct effects upon the Xenopus transcriptome and embryonic development. An RNA-seq based screen was performed to investigate proximal changes to the Xenopus laevis transcriptome in the context of neural development, as a result of iFGFR1 or iFGFR4 activation during a period of early neural specification. After filtering the data, 188 genes were found to be affected by iFGFR1 and 274 genes affected by iFGFR4. As well as genes known to regulate posterior neural development, a number of genes regulating laterality, cell cycle and anterior neural development were also identified as being regulated by both receptors. Functional characterisation of a few novel FGF targets identified from the microarray and/or RNA-seq screens was performed using genome editing approaches. TALEN-mediated knockout of one of these targets, Nek6, was shown to affect the expression of mesodermal and neuroectodermal genes, as well as affecting FGF signalling itself. This work shows that FGFR1 and FGFR4 have distinct signalling outputs during neural development, but cooperate to specify and pattern the developing Xenopus CNS.
Supervisor: Isaacs, Harry Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available