title: Lgr4 is required for Paneth cell differentiation and maintenance of intestinal stem cells ex vivo.
abstract: Gene inactivation of the orphan G protein-coupled receptor LGR4, a paralogue of the epithelial-stem-cell marker LGR5, results in a 50% decrease in epithelial cell proliferation and an 80% reduction in terminal differentiation of Paneth cells in postnatal mouse intestinal crypts. When cultured ex vivo, LGR4-deficient crypts or progenitors, but not LGR5-deficient progenitors, die rapidly with marked downregulation of stem-cell markers and Wnt target genes, including Lgr5. Partial rescue of this phenotype is achieved by addition of LiCl to the culture medium, but not Wnt agonists. Our results identify LGR4 as a permissive factor in the Wnt pathway in the intestine and, as such, as a potential target for intestinal cancer therapy.
authors.affiliation: Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Faculty of Medicine, Université Libre de Bruxelles, Route de Lennik 808, Brussels 1070, Belgium.
authors.forename: Roxana C
authors.initials: RC
authors.lastname: Mustata
authors.forename: Tom
authors.initials: T
authors.lastname: Van Loy
authors.forename: Anne
authors.initials: A
authors.lastname: Lefort
authors.forename: Frédérick
authors.initials: F
authors.lastname: Libert
authors.forename: Sandra
authors.initials: S
authors.lastname: Strollo
authors.forename: Gilbert
authors.initials: G
authors.lastname: Vassart
authors.forename: Marie-Isabelle
authors.initials: MI
authors.lastname: Garcia
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D055786:Gene Knockout Techniques; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000166:cytology; D018021:Lithium Chloride / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009940:Organoids / Q000254:growth & development / Q000378:metabolism; D019879:Paneth Cells / Q000166:cytology*; D010641:Phenotype; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: C496200:LGR4 protein, mouse; C493597:Lgr5 protein, mouse; D043562:Receptors, G-Protein-Coupled; D018021:Lithium Chloride