University of California, San Francisco (UCSF)

Regulation of Pancreatic Morphogenesis in Zebrafish

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Approximately 250 million people worldwide have been diagnosed with diabetes mellitus and that number is growing annually with the increasing obesity epidemic. Both common forms of diabetes, type 1 and type 2, are characterized by a decreased functional beta-cell mass. Strategies to correct the beta-cell deficit include the transplantation of stem-cell or donor derived beta-cells as well as the regeneration of lost beta-cells. Regenerative approaches will require a deep understanding of the mechanisms that instruct pancreatic development to fully restore a functional beta-cell mass in diabetic patients.

We are using zebrafish embryos to study the earliest events in the development of the pancreas and the differentiation of beta-cells. Zebrafish are particularly well suited for these studies because the embryos are optically clear and we can visualize the pancreas in live embryos. We conducted a genetic screen to find novel genes that are important for pancreas development and we are currently analyzing several of the mutants at a molecular and cellular level. In addition we discovered that the pancreas contains distinct populations of beta-cells that differ in therapeutically relevant properties. My future studies are aimed at exploiting the differences between the different sub-types of beta-cells to develop new approaches for the expansion of beta-cell mass.