Figure 7.

Model

1. ISCs divide regularly (“make-to-stock”) and progenitor cells are flexible in delaying their terminal differentiation until detecting a local demand to replace an older or dying epithelial cell. Mechanical input or a chemical signal from the dying cell communicates its state to the neighbouring mesenchymal/progenitor cells that activates mir-8 expression (“make-to-order” stage).
2. The balance between escargot (and zfh1) and miR-8 triggers the mesenchymal-to-epithelial transition (MET) and terminal differentiation to replace a lost enterocyte or enteroendocrine cell.