Regeneration is the ability of organisms to restore their structures in form and function. While it is present in the complete animal kingdom, humans retain the capacity to restore some tissues and organs, but this capacity is limited in comparison with that of other vertebrates such as the zebrafish. Further, the growth of regenerative diseases and the lack of therapies to fully restore damaged organs and limbs highlight the importance of the study of regeneration. To further the understanding of the regeneration process, this study focuses on molecular and cellular dissection of the tail regeneration of zebrafish larvae. The molecular dissection found that the molecular signalling Hedgehog regulates regeneration through the Wnt and Fibroblast Growth Factor (FGF) developmental pathways as follows. The regeneration marker genes msxc, dlx5a and raldh2 are regulated by Hedgehog (Hh) through Wnt signalling, while cell proliferation is regulated by Hh through FGF signalling. Further, the role of Hh during regeneration is unique and different to its role during normal tail development, where it is not essential. Finally, it was found that the muscle differentiation marker myod is expressed sequentially after the regeneration marker genes raldh2 and dlx5a during the late stage of tail restoration. For the cellular dissection cell lineage tracings during regeneration were performed using several Cre expressing lines with tissue specific promoters, where Cre recombination is controlled by 4OH Tamoxifen administration. The lineage tracing analysis showed that both blood vessels and periderm cells participate during tail restoration and that both cell types remain lineage committed. Altogether the results presented in this thesis show that the zebrafish larva tail is a suitable model to study both molecular and cellular aspects of regeneration. The knowledge generated during this PhD research can contribute to set the basis for the development of clinical therapies to assist human regeneration.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:696049 |
| Date | January 2016 |
| Creators | Garcia Romero, Maria Montserrat |
| Contributors | Roehl, Henry Hamilton |
| Publisher | University of Sheffield |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://etheses.whiterose.ac.uk/15398/ |
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