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UBC Theses and Dissertations

Zebrafish as a model to study beta-cell development and regeneration Toselli, Maria Chiara


Diabetes is characterized by insufficient amounts of insulin, a hormone produced by the beta-cells in the pancreatic islets. While current treatment options such as insulin injections provide a way to manage blood glucose levels, these methods provide suboptimal glucose control. Islet transplantation shows significant therapeutic promise, but the lack of available islets is an obstacle for this therapy. Restoration of beta-cell mass through cell therapy or stimulation of endogenous regeneration to replace beta-cell loss and dysfunction could potentially cure diabetes. Hence, investigating beta-cell development and regeneration is extremely valuable. Because zebrafish and mammalian pancreas development are highly conserved, we utilized zebrafish as a model to study beta-cell development and regeneration in the work described in this thesis. We developed and characterized a lineage tracing model that allowed us to differentiate beta-cells arising from the dorsal and ventral pancreatic buds. We lineage traced the dorsal bud derived beta-cells during development until the adult stage. While we observed that dorsal bud derived beta-cells constitute a small percentage of the total beta-cells in the adult pancreas, we did not identify transcriptional differences between beta-cells that arise from dorsal and ventral pancreatic buds, suggesting that developmental origin does not dictate transcriptional profile. Second, we characterized the role of islet vessels during beta-cell formation. We found that islet vessels are dispensable for alpha-cell and beta-cell development. Finally, we determined the cell sources important in beta-cell maintenance and regeneration. We observed that beta-cell proliferation is the main mechanism of beta-cell maintenance in the adult zebrafish, but that a non-beta-cell source may contribute to beta-cell regeneration. By providing a better understanding of zebrafish beta-cell development and regeneration, the findings in this thesis may help guide cell therapies and regenerative strategies for diabetes.

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