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Investigating the role of RNA regulation during zebrafish embryonic development
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Leech, Rebecca (2023) Investigating the role of RNA regulation during zebrafish embryonic development. PhD thesis, University of Warwick.
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Official URL: http://webcat.warwick.ac.uk/record=b3986120
Abstract
For precise embryonic body plans to form, tight spatiotemporal control of molecules, pathways and morphological changes is required. Spatial information is communicated through highly conserved signalling pathways. One such pathway is the Nodal signalling pathway. Nodal signalling is required for mesoderm and endoderm formation, two of the primary germ layers. Moreover, Nodal signalling controls left-right asymmetry of vertebrate visceral organs. In zebrafish, two RNA-binding proteins have been established as nodal mRNA binders, regulating localisation and expression at early developmental stages. Ybx1 and Igf2bp3 are required for normal embryonic and germline development. Two of the earliest specified tissues in zebrafish embryos are the progenitor germ cells and the extra-embryonic yolk syncytial layer. Both of these are abnormal in ybx1 and igf2bp3 mutants. Moreover, Nodal signalling is elevated in these mutants. However, the precise molecules and pathways through which they act have yet to be determined. In this thesis, I identified misregulated genes in igf2bp3 mutants by RNAsequencing. I showed there is a reduction in germline components, as well as misregulated chemokine signalling, which is required for progenitor germ cell migration. Moreover, I showed there is elevated Nodal signalling and elevated YSL markers, consistent with the expanded YSL phenotype. To determine novel genes which may be important for YSL formation, I identified yolk-enriched transcripts through embryo dissections and RNAsequencing. By comparing YSL mutants and yolk-enriched genes, as well as direct targets of Igf2bp3, I reported a list of genes with potential YSL roles. In particular, I have identified Micall2a, a cytoskeletal regulator and Rab interactor. This is a highly conserved protein, known to regulate endocytic recycling and cell-cell junction formation in human cells. Further work will reveal Micall2a’s role in YSL formation. Moreover, the expression of Micall2a in human placental syncytiotrophoblasts raises interesting questions regarding conserved mechanisms of syncytia formation.
Item Type: | Thesis (PhD) | ||||
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Subjects: | Q Science > QH Natural history > QH426 Genetics Q Science > QL Zoology |
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Library of Congress Subject Headings (LCSH): | Zebra danio -- Embryos, Genetic regulation, RNA, RNA-protein interactions, Germ cells, Embryology | ||||
Official Date: | May 2023 | ||||
Dates: |
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Institution: | University of Warwick | ||||
Theses Department: | Warwick Medical School | ||||
Thesis Type: | PhD | ||||
Publication Status: | Unpublished | ||||
Supervisor(s)/Advisor: | Sampath, Karuna, 1967- ; Hebenstreit, Daniel, 1977- | ||||
Sponsors: | Medical Research Council (Great Britain) | ||||
Format of File: | |||||
Extent: | 208 pages : colour illustrations | ||||
Language: | eng |
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