Figure 7. Local injury to the gut mucosa and subsequent reconstitution of crypt-villus architecture.

Panel A displays populations of living gut epithelial cells (GECs) on the crypt and villus, and necrotic cells upon local tissue injury and subsequent healing. Injury is induced by causing necrosis of an entire villus, resulting in a rapid drop of villus GEC population and spike in necrotic cell population (Arrow 1). In the time period directly subsequent to villus death the crypt grows rapidly; this is due to the sudden loss of Sonic Hedgehog Homolog (Hh) signaling as most of the differentiated cells on the villus have died. The death of the villi cells reduces the Wnt inhibition of the surviving crypt GECs, resulting in a growth spike in the crypt population (Arrow 2) that precedes the reconstitution of the villus population (Arrow 3). All during this process the inflammatory response is clearing the necrotic cells, allowing the regulatory functions of the morphogen pathways to normalize, leading to regrowth of the villus back to the homeostatic state (Arrow 4). Panels B–D display three screenshots from a simulation of localized epithelial damage/injury. Undifferentiated transit amplifying (TA) cells are shaded in blue. Differentiated enterocytes are shaded in red. Necrotic cells are shaded in black. Panel B, captured at t = 750 min, demonstrates that the epithelial insult results in necrotic cell death throughout the majority of the villus. Panel C, captured at t = 2250 min, shows that the necrotic cells continue to damage surrounding tissue until clearance by macrophages and neutrophils (not explicitly represented in these screenshots). Panel D, captured at t = 4500 min, demonstrates the recovered tissue architecture after regrowth of the epithelial cell populations.