Hydrogen peroxide (H2O2) is produced following injury and is required for regeneration. However, how H2O2 coordinates multiple signalling pathways required for regeneration is not known. Protein... Show moreHydrogen peroxide (H2O2) is produced following injury and is required for regeneration. However, how H2O2 coordinates multiple signalling pathways required for regeneration is not known. Protein-tyrosine phosphatases (PTPs) are regulators of signal transduction, reversing the phosphorylation of substrates, and are essential for many cellular processes. PTPs are also highly sensitive to reversible oxidation-mediated inhibition by H2O2.My research identified that some, but not all, PTPs become oxidized following amputation of the zebrafish caudal fin, and implicates PTPs that are oxidized as necessary for the regenerative process. Furthermore, I delineated that the PTPs Shp2 and Pten are required for the regenerative outgrowth phase of regeneration, and that Shp2 and Pten have a role in driving MAPK signalling and balancing PI3K signalling, respectively, during this phase. Show less
The aim of this thesis was to investigate the expression, and function of genes associated with remodelling and regeneration in the zebrafish model species. Here, we studied the role of cell... Show moreThe aim of this thesis was to investigate the expression, and function of genes associated with remodelling and regeneration in the zebrafish model species. Here, we studied the role of cell populations, defined by their expression of markers, in bone regeneration and remodelling in zebrafish embryos and adult zebrafish scales. We used mesoporous silica nanoparticles to carry cytokines, known to activate hematopoietic cells into osteoclasts, into tissues of the living embryo. We further investigated the role of genes such as matrix metalloproteinases in regeneration of adult zebrafish scales. These genes are known to be involved in matrix degradation and have been found to be expressed in mammalian osteoclasts. We studied both by in situ hybridisation and immunocytochemistry the presence of mononucleated and multinucleated mmp-9 positive cells on the episquamal side of adult zebrafish scales. Finally we studied the regeneration of the caudal fin of zebrafish embryos with a special emphasis on the effect of glucocorticoids on regeneration and wound healing. Glucocorticoids in this case mimic stress conditions in the embryos, thus helping understand the effect of early exposure to stress on wound healing and tissue Remodelling. Show less
