Blueprint for an intestinal villus: Species‐specific assembly required

• Published in: Wiley interdisciplinary reviews. Developmental biology 2018-07, Vol.7 (4), p.e317-n/a
• Main Authors: Walton, Katherine D., Mishkind, Darcy, Riddle, Misty R., Tabin, Clifford J., Gumucio, Deborah L.
• Format: Article
• Language: English
• Subjects: Animals; Cell proliferation; Embryogenesis; Endoderm; Enteric nervous system; Epithelial cells; Epithelial Cells - physiology; Epithelial Cells - ultrastructure; epithelial‐mesenchymal cross‐talk; Epithelium; fetal intestine; Fetuses; Fibroblasts; Humans; Intestinal Mucosa - cytology; Intestinal Mucosa - embryology; Intestinal Mucosa - physiology; Intestine; Mesenchyme; Mice; Microvilli - physiology; Morphogenesis; Nerves; Nutrients; Organogenesis; Organogenesis - physiology; Rats; Signal Transduction; Smooth muscle; Species; Species Specificity; Stem cells; Villus; villus development
• ISSN: 1759-7684; 1759-7692
• DOI: 10.1002/wdev.317

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. Efficient absorption of nutrients by the intestine is essential for life. In mammals and birds, convolution of the intestinal surface into finger‐like projections called villi is an important adaptation that ensures the massive surface area for nutrient contact that is required to meet metabolic demands. Each villus projection serves as a functional absorptive unit: it is covered by a simple columnar epithelium that is derived from endoderm and contains a mesodermally derived core with supporting vasculature, lacteals, enteric nerves, smooth muscle, fibroblasts, myofibroblasts, and immune cells. In cross section, the consistency of structure in the billions of individual villi of the adult intestine is strikingly beautiful. Villi are generated in fetal life, and work over several decades has revealed that villus morphogenesis requires substantial “crosstalk” between the endodermal and mesodermal tissue components, with soluble signals, cell–cell contacts, and mechanical forces providing spe