Analysis of early endoderm development in the mouse

During organogenesis, the endoderm forms the primitive gut tube, from which thymus, thyroid, lung, liver and pancreas are derived. Defining the key events of endoderm development will be beneficial in identifying targets in human disease and is fundamental in deriving organ progenitors from embryonic stem (ES) cells for cell-replacement therapy.

One crucial component of our work is the establishment of an ex vivo endoderm formation assay, by genetically and embryologically labeling endoderm lineages (see Figure) in a static embryo culture system (see movie).

Real-time imaging will give first insights into the morphogenetic processes associated with endoderm germ layer formation and will reveal how mutations affect endoderm development. To understand how endoderm patterning translates into organ formation cell-lineage tracing will be used to follow the fate of distinct endoderm precursor cell populations. Conditional inactivation of developmental regulatory signaling cascades in these precursor cells will shed light on signals directing early endoderm lineage decisions.

Moreover, genome-wide expression profiles of endoderm mutants were and are used as a basis for a large-scale in situ expression screens to identify novel components and marker genes of early endoderm development (see bottom of the Figure). The function of these genes during endoderm development will be tested by transgenic RNA interference (RNAi)-mediated knockdown and conventional gene targeting approaches. Combining these gene functional studies with the above mentioned ex vivo endoderm formation assays provides an efficient way to analyze endoderm mutant phenotypes in real time and on a cellular level.