再生生物学中一个基本但未解决的问题是组织在受损后如何恢复到稳态。回答这个问题对于理解炎症性肠病和癌症等慢性疾病的病因是至关重要的。我们使用果蝇中肠来研究这个问题，并发现在再生过程中，胆碱能肠神经元的一个亚群通过调节肠上皮细胞的Ca2+电流来促进上皮恢复到稳态。具体而言，我们发现上皮中胆碱酯酶乙酰胆碱酯酶的下调使特定的肠道神经元（称为ARCENs）释放的乙酰胆碱能够激活ARCEN-周围的上皮细胞中的肌动蛋白受体。这种激活引发了高水平的Ca2+流入，通过Inx2/Inx7缝隙连接在上皮中蔓延，促进上皮细胞成熟，随后减少增殖和炎症反应。破坏这个过程会导致离子失衡、Yki激活以及炎症因子增加，同时伴有增生，类似于炎症性肠病。总之，我们发现在肠道再生过程中，保守的胆碱能途径促进上皮Ca2+波，从而治愈肠道上皮。我们的发现展示了神经和生物电依赖的肠道再生，推进了对组织在受损后如何返回稳态状态的理解，并最终有助于现有疗法的发展。

A fundamental and unresolved question in regenerative biology is how tissues return to homeostasis after injury. Answering this question is essential for understanding the etiology of chronic disorders such as inflammatory bowel diseases and cancer. We used the Drosophila midgut to investigate this question and discovered that during regeneration a subpopulation of cholinergic enteric neurons triggers Ca 2+ currents among enterocytes to promote return of the epithelium to homeostasis. Specifically, we found that down-regulation of the cholinergic enzyme Acetylcholinesterase in the epithelium enables acetylcholine from defined enteric neurons, referred as ARCENs, to activate nicotinic receptors in enterocytes found near ARCEN- innervations. This activation triggers high Ca 2+ influx that spreads in the epithelium through Inx2/Inx7 gap junctions promoting enterocyte maturation followed by reduction of proliferation and inflammation. Disrupting this process causes chronic injury consisting of ion imbalance, Yki activation and increase of inflammatory cytokines together with hyperplasia, reminiscent of inflammatory bowel diseases. Altogether, we found that during gut regeneration the conserved cholinergic pathway facilitates epithelial Ca 2+ waves that heal the intestinal epithelium. Our findings demonstrate nerve- and bioelectric-dependent intestinal regeneration which advance the current understanding of how a tissue returns to its homeostatic state after injury and could ultimately help existing therapeutics.