The knowledge about pancreas development and the establishment of pancreatic cell lineages has exploded in recent years. These studies are important in developing strategies for regenerative medicine. On the other hand, pancreatic ductal adenocarcinoma (PDAC) is the tumor with the worst prognosis in humans: its incidence rate is equivalent to its mortality rate, with a median survival of less than 6 months. In this project, we will use retrospective clonal analysis to analyze the clonal structure of the mouse pancreas. Unlike other lineage tracing studies, the technique proposed allows the analysis of individual, low-frequency, clones. By doing this we pretend to dealwith questions such as clonality, clonal size and clonal variation in the embryonic pancreas. Moreover, we aim at developing strategies to analyze quantitatively the adult pancreas, not only in normal conditions but also in situations where the pancreas structure is disrupted by disease. We will thus use models of experimental pancreatitis. In the final step of this project, we pretend to set up the basis to use our clonal approach with murine PDAC murine models, using both genetic mouse models and carcinogen treatment. The work will impy two host groups with distinct and complementary expertise: developmentl biology and pancreas cancer biology. This kind of approach will become important in cancer research in the future in order to understand clonal evolution. The proposed project builds on the experience of the candidate and will allow him to acquire new expertise in cancer biology in order to establish his scientific career in the future.