Endocrine Abstracts

The formation of the vertebrate pancreas is a complex process that typifies the basic steps of embryonic development. It involves the establishment of competence, specification, signaling from neighboring tissues, morphogenesis, and the elaboration of tissue-specific genetic networks. A full analysis of this multistep process will help us to understand classic principles of embryonic development. Furthermore, this will provide the blueprint for experimental programming of pancreas formation from embryonic stem cells in the context of diabetes cell-therapy. 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. This is particularly true for stages between endoderm formation and initiation of organogenesis.

Combining embryology and genomics in Xenopus laevis, we have characterized these early stages and identified: 1) a suite of early endodermal factors that establish a pancreatic pattern within the pluripotent endoderm, including the transcriptional modulator, TGIF2; and 2) an instructive signal sufficient to induce pancreatic differentiation and, notably, insulin expression in the embryo, such as the signaling factor, Shirin/DLC2. Subsequently, using a comparative developmental approach, we have showed that the biological activity of these novel inductive pancreatic signals is conserved in mammalian systems.

These findings implicate new and unexplored pathways in the early stages of pancreas formation. Further investigation of the biological function of these factors and integration into the network of previously defined determinants will elucidate the early mechanisms coming into play to pattern the pre-pancreatic region within the endoderm and, gradually, specify the pancreatic tissue.