Differentiation of the Endoderm Lineage in the Murine System

The endoderm is one of the three principle germ layers that arise during gastrulation in early embryonic development. In the course of development it gives rise to functionally diverse organs, e.g. thymus, lung, liver, pancreas, stomach and the gastrointestinal tract. The main research topic was the analysis of the endoderm differentiation in murine embryonic stem cells (ES cells) and embryos. The generation and analysis of two knock-in Cre mouse lines for two endodermally expressed transcription factors are described here. The analysis comprises studies of Cre recombination pattern as well as studies regarding the influence of the Foxa2 hypomorhic mutation on metabolism. On the basis of the obtained data the existence of two different promotors could be shown and the tissue-specific expression of the resulting mRNA isoforms could be confirmed. Furthermore an in vitro endoderm differentiation system for ES cells was established and characterized. Using this system the influence of different micro RNAs (miRNAs) on ES cell differentiation was investigated. This way two miRNAs (miR335 and miR194) were identified that regulate Foxa2 translation and thereby endoderm differentiation.