Examination of neuroregulation in intestinal epithelium using stem cell differentiation-visualizing mice

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Vasoactive intestinal peptide (VIP), a neurotransmitter, is released by the parasympathetic neurons in the small intestine. Epithelial stem cells (ESCs) reside at the epithelial layer of crypts in the small intestine and are directly intermingled with Paneth cells which provide a suitable environment for the ESCs.In the present study, VIP-positive neurons were detected approximately under subepithelial mesenchymal cells. It was also found that VIP receptors (VPAC1R) were expressed on Paneth cells but not on the ESCs. When VIP was added to a three-dimensional organoid culture system of intestinal crypts, the formation of organoids was inhibited in a dose-dependent manner. It was previously reported that VPAC1R-knockout mice had the hyper-proliferative intestinal epithelium. From the result reported and the present findings, it is conceivable that VIP is a physiological neuroregulatory factor which regulates negatively the proliferation/differentiation of ESCs.