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Enteroendocrine cell lineages that differentially control feeding and gut motility.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Kaye, Judith A 
Douglas, Ella R 

Abstract

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.

Description

Funder: Food Allergy Initiative

Keywords

appetite, enteroendocrine cell, gut-brain axis, intersectional genetics, mouse, neuroscience, single-cell RNA sequencing, Mice, Animals, Enteroendocrine Cells, Cell Lineage, Glucagon-Like Peptide 1, Gastric Inhibitory Polypeptide, Cholecystokinin

Journal Title

Elife

Conference Name

Journal ISSN

2050-084X
2050-084X

Volume Title

12

Publisher

eLife Sciences Publications, Ltd
Sponsorship
Medical Research Council (MC_UU_12012/3)
MRC (MC_UU_00014/3)
MRC (MC_UU_00014/5)
Medical Research Council (MC_PC_12012)
Wellcome Trust (220271/Z/20/Z)