A fundamental question in developmental biology is how a specialized tissue or organ originates from a pluripotent precursor cell in the embryo. The central aim of my research is to understand how and when the pancreas is progressively specified during embryogenesis. The pancreas controls two crucial functions in our body: the production of digestive enzymes and the regulation of blood sugar. Although in the past decade many studies have contributed to a solid foundation for understanding pancreatogenesis, important gaps persist in our knowledge of early pancreas formation. A complete understanding of these early events will provide insight into the development of this organ, but also into incurable diseases that target the pancreas, such as diabetes. Finally, this information will generate a blueprint for developing cell-replacement therapies in the context of diabetes.
My postdoctoral research has provided important insight into the early steps of pancreatic specification. Combining embryology and genomics in Xenopus laevis, I have identified a suite of early pancreatic factors that establish pancreatic fate within the pluripotent endoderm, including a novel signaling factor, that we named Shirin. Importantly, Shirin is alone sufficient to induce pancreatic fate and, notably, insulin expression in the embryo. In addition, Shirin is one of the earliest markers identified as being expressed in the forming pancreas both in frog and mouse embryos. To address the relevance of Shirin in the context of mammalian development and understand its mechanism of action and epistatic relations within the previously known pancreatic network, I plan to: (i) In vivo study the role of Shirin in the mouse developing pancreas by loss-of-function approach; (ii) In vitro study the potential role of Shirin in triggering differentiation towards pancreatic fate using mouse embryonic stem cells, as powerful system for in vitro dissection of mammalian embryonic development.
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