Emergence of the Endoderm in the Mammalian Embryo: From Cell Fate Specification to Gut Tube Formation

The endoderm is the embryonic tissue that gives rise to vital organ systems in both the developing embryo and adult animal. Cells with a definitive (embryonic) endoderm identity emerge from the pluripotent epiblast at gastrulation, and go on to form the gut tube, which develops into the epithelial component of the digestive and respiratory tracts. In this review, we discuss the mechanisms driving endoderm emergence and morphogenesis, including key epithelial-mesenchymal and mesenchymal-epithelial transitions, the mechanical forces driving gut tube formation, and the patterning events that subdivide the gut tube into different organ territories. We also elaborate on the role of the primitive endoderm, which emerges earlier at the blastocyst stage and contributes mainly to extraembryonic tissues in amniotes—such as the yolk sacs—essential for the embryo's nutrition and protection. Together, this review provides an overview of the current understanding of early endoderm development and highlights key open questions.