Research Report 2010 - MDC

Francesca M. SpagnoliStructure of the GroupGroup LeaderDr. Francesca M. Spagnoli**ScientistsDr. Elisa Rodríguez Seguel**part of the period reported** start of the group: July 2008Graduate StudentsNuria Cerdá-Esteban*Kristin Petzold*Igor Pongrac*Technical AssistantsHeike Naumann*Molecular and Cellular Basis ofEmbryonic DevelopmentAfundamental question in developmental biology is how a specialized tissue originatesfrom a pluripotent precursor cell in the embryo. The endoderm germ layer gives rise to anumber of vital organs in our body, including the lungs, liver, pancreas and intestine. Thisremarkable diversity derives from a homogenous and multipotent precursor cell population.The central aim of our research is to understand the mechanisms that pattern and establishcompetence within anterior embryonic endoderm in order to progressively specify thepancreatic organ domain. In addition, we focus on spatio-temporal mechanisms that restrictspecification of the pancreas versus neighboring tissues, such as the liver. A completeunderstanding of these early events will provide insights into the development of theseorgans. Finally, this information might be crucial for advances in regenerative medicinestrategies for the treatment of incurable diseases, such as diabetes.ProjectsIn vivo lineage analysis of pancreatic and hepaticprecursor cellsElisa Rodríguez Seguel, Igor PongracDuring embryogenesis, the pancreas originates fromdistinct outgrowths of the dorsal and ventral foregutendoderm. Both outgrowths give rise to endocrine andexocrine cells and, subsequently, fuse to form one singleorgan. The ventral pancreas arises next to thehepatic endoderm and they possibly originate from acommon bipotent precursor. However, a single cell havingthe dual potential to differentiate along the hepaticand pancreatic lineages has never been isolated neitherin vivo nor in vitro. One main focus of my laboratoryis to investigate how pancreatic versus hepatic fatedecision occurs in the endoderm at both the cellularand molecular level.To conduct a comprehensive in vivo analysis of thehepatic-pancreatic lineage in the mouse embryo, weuse transgenic reporter models that express EGFP orphotoconvertible fluorescent proteins under the controlof lineage-specific promoters. We are using thesenew genetic tools to: i. address in vivo and in vitro if theliver and pancreas arise from a common bipotent precursor;and ii. to trace and molecularly profile the presumptiveprecursor cell and its descendants in themouse embryo. All together, these experiments willdetermine how the hepatic-pancreatic lineage is establishedin vivo, whether a bipotent endodermal precursorexists, and provide us with its molecular signature.Molecular mechanisms controlling pancreas versusliver fate decisionNuria Cerdá-Esteban, Heike NaumannHepatic and pancreatic endoderm share a common setof intrinsic regulatory factors, such as the FoxA andGATA transcription factors, and are exposed to the sameextrinsic signals, FGF and BMP. However, it remainsunclear how the same factors can activate pancreaticgenes, such as Pdx1 and Ptf1a, in the future pancreas,without inducing them in hepatic progenitors; andanalogously, they enable liver development, but notpancreatic development in the hepatic endoderm. Both22 Cardiovascular and Metabolic Disease Research