Development and regeneration of insulin-producing β cells: Diabetes is associated with a loss of β cells. The goal of the Parsons lab is to find therapeutic routes that can increase β-cell numbers and reverse a diabetic state. We utilize the zebrafish as a model system in order to expedite the discovery of the mechanisms that regulate the production of β cells from stem cells (neogenesis).
Zebrafish are an ideal system to study vertebrate embryogenesis, as they are genetically tractable and have transparent, externally developing embryos. Easy transgenesis allows specific cells and their behaviors to be visualized within living animals. Moreover, with their small size and high fecundity, the zebrafish represents the only tangible method to perform high-throughput chemical screening on a living, intact vertebrate organism. The Parsons lab was part of a collaborative effort that carried out the first truly high-throughput chemical screen on zebrafish larvae. What makes the zebrafish particularly compelling for research into β-cell neogenesis is that zebrafish pancreatic cells readily regenerate following damage. Consequently this model system provides two separate opportunities to experimentally manipulate and study β-cell neogenesis—namely, development and regeneration. We have identified the β-cell progenitor during both development and regeneration; these specialized cells are called centroacinar cells and are found in the pancreatic ducts of all vertebrates, including humans.
Building on this work, we are now discovering the molecular mechanisms that regulate the differentiation of centroacinar cells to β cells that occurs during zebrafish β-cell regeneration. This knowledge will reveal the pathways that should be pharmacologically induced in human tissues to facility human β-cell regeneration.
