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Research

During embryogenesis cells of the developing organism become progressively restricted in their developmental potential. Pluripotent cells of the epiblast get specified to different lineages according to their position within the embryo at certain critical time points to establish the various different cell types of the body. This initial lineage restriction also defines the primary body pattern, lays down the set of different cell types required for all following steps during development and is maintained throughout the entire lifespan. Lineage specification is influenced by dynamic cell-cell interactions and extracellular stimuli - e.g. growth-factors or extracellular components – to define the route of cells from stem- and progenitor cells to terminal differentiation.

Our group is mainly interested in the processes that shape the embryo during the time when pluripotent progenitor cells of the epiblast become specified to the three germ layers, namely ectoderm, mesoderm and endoderm. We aim to contribute to the understanding of this gastrulation process by using combinations of mouse genetics, embryo imaging techniques and in vitro cell culture systems. Enhancing current knowledge of early cell type specification events will be instrumental in developing new strategies to use stem- and progenitor cells, such as embryonic stem (ES) cells and induced pluripotent cells (iPCs) for novel approaches in regenerative medicine and tissue replacement.

In previous work we were able to identify the T-box transcription factor Eomesodermin (Eomes) as a central player for the specification of definitive endoderm and morphogenesis of the mesoderm cell layer. While the phenotype of Eomes mutants is striking the mechanistic understanding of Eomes regulated processes has yet to be established. Therefore our future goals are:

1. The identification of transcriptional targets and regulatory hierarchies of Eomes regulated processes during germ layer formation.

2. The extended and detailed analysis of germ-layer formation in wildtype and Eomes-mutant embryos using live, real-time embryo imaging techniques to visualize cell behaviour during the dynamic process of gastrulation.

3. Development of cell culture systems to specifically generate and analyse sub-populations of endoderm and mesoderm progenitor cells from pluripotent cells.

 

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