TY - JOUR TI - Enteroendocrine cell lineages that differentially control feeding and gut motility AU - Hayashi, Marito AU - Kaye, Judith A AU - Douglas, Ella R AU - Joshi, Narendra R AU - Gribble, Fiona M AU - Reimann, Frank AU - Liberles, Stephen D A2 - Chesler, Alexander Theodore A2 - VijayRaghavan, K A2 - Chesler, Alexander Theodore VL - 12 PY - 2023 DA - 2023/02/22 SP - e78512 C1 - eLife 2023;12:e78512 DO - 10.7554/eLife.78512 UR - https://doi.org/10.7554/eLife.78512 AB - Enteroendocrine cells are specialized sensory cells of the gut-brain axis that are sparsely distributed along the intestinal epithelium. The functions of enteroendocrine cells have classically been inferred by the gut hormones they release. However, individual enteroendocrine cells typically produce multiple, sometimes apparently opposing, gut hormones in combination, and some gut hormones are also produced elsewhere in the body. Here, we developed approaches involving intersectional genetics to enable selective access to enteroendocrine cells in vivo in mice. We targeted FlpO expression to the endogenous Villin1 locus (in Vil1-p2a-FlpO knock-in mice) to restrict reporter expression to intestinal epithelium. Combined use of Cre and Flp alleles effectively targeted major transcriptome-defined enteroendocrine cell lineages that produce serotonin, glucagon-like peptide 1, cholecystokinin, somatostatin, or glucose-dependent insulinotropic polypeptide. Chemogenetic activation of different enteroendocrine cell types variably impacted feeding behavior and gut motility. Defining the physiological roles of different enteroendocrine cell types provides an essential framework for understanding sensory biology of the intestine. KW - gut-brain axis KW - single-cell RNA sequencing KW - intersectional genetics KW - appetite KW - enteroendocrine cell JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -