At the end of gastrulation, the endoderm forms the ventral surface of the developing embryo. Subsequently, through a series of poorly understood morphogenetic events, the initially flat endoderm is transformed into the gut tube, a cylindrical structure that gives rise to the epithelial lining of the entire respiratory and gastrointestinal tracts. At present there is no mechanistic understanding of how the endoderm is transformed from a planar sheet to a simple tube. In avian and mammalian species, formation of the gut tube begins with two invaginations at the anterior and posterior poles of the embryo, termed the anterior (AIP) and caudal intestinal portals (CIP). The AIP, which forms the foregut, and CIP which forms the hindgut, begin moving toward one another, “zipping” the gut tube closed along the embryonic midline (Fig. 1A). The AIP and CIP meet at the umbilicus (mammals) or yolk stalk (avian), where the midgut is formed.

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