At the end of gastrulation, the endoderm forms a single-cell thick epithelium lining the ventral surface of the developing embryo. Subsequently, through a series of poorly understood 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. In birds and mammals, formation of the gut tube begins with two invaginations at the anterior (head) and posterior (tail) poles of the embryo, termed the anterior (AIP) and caudal intestinal portals (CIP). It is thought that the AIP and CIP begin moving toward one another as two progressing waves of lateral-to medial folding (from left and right toward center), “zipping” the gut tube closed along the embryonic midline (Fig. 1A). This view of lateral-to-medial folding is, however, inconsistent with several observations. For example, fate mapping studies in chick and mouse that suggest that cells originating in the posterior end (toward the tail) of the flat endoderm do not form the hindgut, but instead contribute to the more anterior midgut [1, 2]. This would not be possible in a simple lateral-to-medial folding process. Therefore, it is largely unknown how this fundamental structure of the vertebrate body plan is established. The objective of the present work is to apply multi-photon live imaging of the chick embryo to determine how the hindgut is formed. Our findings suggest the hindgut arises from directed, collective cell movements that drive antero-posterior folding of the initially flat endoderm.

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