Molecular analysis of cell fate specification in mouse gastrulation

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Embryonic development from the fertilized egg to adulthood is achieved by successive steps of cell lineage -restriction and -determination events from pluripotent progenitor cells leading up to terminal differentiation. During early development the primary germ layers ectoderm, mesoderm and endoderm are specified from a common progenitor tissue, namely the epiblast, under the complex control of graded signalling molecules, such as Wnts, TGFb/BMPs and FGFs2, 3. Signalling inputs are interpreted intracellulary and orchestrate the genetic program and cellular response underlying the differentiation processes. Whereas the important signalling molecules and corresponding pathways were previously identified, the molecular details of genetic programs and changes in cell behaviour leading to germ layer specification remain ill defined. We previously uncovered the crucial role of the transcription factor Eomesodermin (Eomes) during the early phase of endoderm formation and morphogenesis of the mesoderm cell layer1. This work program proposes to analyse the function of Eomes at the molecular level and to use the results as an entry point to decipher the regulatory network guiding the gastrulation process during early mammalian embryogenesis. A combination of genetic approaches in mouse and in vitro differentiation studies of embryonic stem (ES) cells will be employed. Expected findings will have significant implications for the differentiation of stem and progenitor cells into different tissue types and will enhance the options for stem cell therapy and regenerative medicine.