Cholinergic neuro-epithelial interactions and gap junctions spread Ca2+ across the intestinal epithelium to promote homeostasis after injury

How a tissue returns to homeostasis following injury remains enigmatic. Here, we show that elevated Ca2+ dynamics among enterocytes (ECs) mediated by nAchRs (nicotinic Acetylcholine (Ach) Receptor) in the adult Drosophila midgut, are essential for the epithelium to return to homeostasis after injury. This bioelectric signal is controlled by 1) changes in EC-responsiveness to Ach; 2) enteric neuro-EC interactions; and 3) epithelial gap junctions. Our findings demonstrate how a bioelectric signal during regeneration, initiated by local neuro-epithelial communication and propagated by gap junctions, is coupling the epithelium into a unified response that promotes return to homeostasis. 10x single-nuclei RNA-sequencing of adult Drosophila gut