Blueprint for an intestinal villus: Species‐specific assembly required

Prior to villus morphogenesis, the chick and mouse intestines both begin as a flat epithelial tube (blue) composed of thick pseudostratified endodermally derived cells surrounded by loose mesenchyme (light pink). By E6 in the chick, these thick epithelial cells shorten, taking on a more columnar shape and, with the confinement by organization of the outer circumferential muscle layer (red) at E8, they begin bending to create ridges that run length‐wise. With the addition of longitudinal muscle at E13, the ridges are transformed into zigzags, and finally by E16, a third layer of longitudinal muscle in direct apposition to the epithelium provides a final compressive force driving emergence of villi from the zigzags. In the mouse, villus emergence is not coordinate with sequential muscle layer development. Instead, villus emergence is initiated when aggregations of mesenchymal cells (clusters, dark pink) form adjacent to the thick pseudostratified epithelium under the direction of epithelial signals (purple). These clusters are highly patterned and together with forces within the epithelium between the clusters driven by cell division at the luminal side that extend the apical surface (T‐invaginations), villi are separated. Signals from the cluster instruct abutting epithelium to withdraw from the cell cycle and shorten, taking on a columnar shape. Epithelial cells between the clusters remain pseudostratified and highly proliferative, thus creating the intervillus domains.