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Title: Retinoid signalling in Xenopus neural development
Author: Fourla, Danai-Dionysia
ISNI:       0000 0001 3478 5908
Awarding Body: University of Portsmouth
Current Institution: University of Portsmouth
Date of Award: 2006
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This thesis focuses on the use of animal caps to address questions concerning neural induction, patterning and neurogenesis in Xenopus embryos. Animal caps can be neuralised by the inhibition of BMPs through the action of inhibitors, such as noggin, but they do not form neurons. Instead, primary neurogenesis requires additional signalling by retinoic acid (RA), acting through the retinoid receptors, RARIRXR. In the presence of RA, retinoid signalling (RS) activates gene expression. Key target genes of RS during development are the Hox genes that are believed to be important for both posterior patterning and neurogenesis. In contrast, in the absence of RA, RS promotes active repression; a process that is required for normal head formation. However, much less is known of the genes that are affected by active repression. Although RS is sufficient to promote neurogenesis in noggin-neuralised animal caps, it is likely to be working in conjunction with other, endogenous, signalling pathways, mediated for example by FGF and Wnt. In this study, animal caps were analysed for signalling molecule expression after neuralisation by noggin and treatment with RARlRXR (±RA) and it was shown that the expression of some, but not all, FGFs and Wnts respond to RS in the animal cap. This may be significant for neural induction, patterning and neurogenesis; related processes in the animal cap. In addition, the receptor isotypes RARa and RARy seem to elicit different responses from some genes. Positive RS (RARlRXR+RA) was shown to promote posterior markers, such as Hox genes and the expression of Wnt3A. However, negative RS (RARlRXR-RA) was shown to inhibit Wnt3A and activate xSaiF. Consequently, RARs promote Wnt signalling posteriorly via positive signalling and inhibit Wnt signalling anteriorly by negative signalling. In conclusion, this thesis shows that animal caps can be used to investigate the effects of RS in Xenopus neural development and indicates a major role for RS along the length of the AlP axis of the embryo.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available