Cell behaviors and molecular mechanisms directing gut endoderm morphogenesis in the mouse embryo

The cell behaviors underlying the morphogenesis of the gut endoderm, the tissue that will give rise to the respiratory and digestive tracts and associated organs, are complex and not well understood. By combining live imaging and genetic labeling, we have visualized the dynamic cell behaviors during endoderm formation in the mouse embryo. Our observations have led us to propose a new model of endoderm morphogenesis in which an epiblast-derived cell population intercalates with the pre-existing visceral endoderm epithelium by an egression-mediated cell dispersal event. This leads to extensive cell mixing on the surface of the embryo and results in the gut endoderm comprising cells of two distinct origins.To gain mechanistic insight into the dynamics of gut endoderm formation, we have begun to characterize the stereotypical sequence of events required for this process both in wild type embryos and mutants in which different steps of the process are affected.Elevated rates of cell proliferation in the epiblast and its derivatives as compared to the overlying visceral endoderm could provide a driving force for remodeling of visceral endoderm cell junctions and egression of epiblast-derived cells onto the surface of the embryo. Epithelial-to-mesenchymal transition (EMT) and cell delamination at the primitive streak could provide both a trajectory and appropriate morphology for egressing cells, which then undergo a mesenchymal-to-epithelial transition (MET) as they intercalate with visceral endoderm-derived cells. Acquisition of endoderm-specific marker expression in combination with the remodeling of basement membrane could reveal a commitment for egression and subsequent re-epithelialization (MET) of cells.