title: Contractile forces at tricellular contacts modulate epithelial organization and monolayer integrity.
abstract: Monolayered epithelia are composed of tight cell assemblies that ensure polarized exchanges. EpCAM, an unconventional epithelial-specific cell adhesion molecule, is assumed to modulate epithelial morphogenesis in animal models, but little is known regarding its cellular functions. Inspired by the characterization of cellular defects in a rare EpCAM-related human intestinal disease, we find that the absence of EpCAM in enterocytes results in an aberrant apical domain. In the course of this pathological state, apical translocation towards tricellular contacts (TCs) occurs with striking tight junction belt displacement. These unusual cell organization and intestinal tissue defects are driven by the loss of actomyosin network homoeostasis and contractile activity clustering at TCs, yet is reversed by myosin-II inhibitor treatment. This study reveals that adequate distribution of cortical tension is crucial for individual cell organization, but also for epithelial monolayer maintenance. Our data suggest that EpCAM modulation protects against epithelial dysplasia and stabilizes human tissue architecture.
authors.affiliation: Cell Adhesion and Mechanics, Institut Jacques Monod, CNRS UMR7592, Paris Diderot University, 75205 Paris, France.|Department of Paediatric Gastroenterology, Hôpital Necker-Enfants Malades, Sorbonne Paris Cité, 75015 Paris, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Salomon
authors.affiliation: Cell Adhesion and Mechanics, Institut Jacques Monod, CNRS UMR7592, Paris Diderot University, 75205 Paris, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Gaston
authors.affiliation: Cell Adhesion and Mechanics, Institut Jacques Monod, CNRS UMR7592, Paris Diderot University, 75205 Paris, France.
authors.forename: Jérémy
authors.initials: J
authors.lastname: Magescas
authors.affiliation: Morphogenesis, Homoeostasis and Pathologies, Institut Jacques Monod, CNRS UMR7592, Paris Diderot University, 75013 Paris, France.
authors.forename: Boris
authors.initials: B
authors.lastname: Duvauchelle
authors.affiliation: Department of Paediatric Anatomo-Pathology, Hôpital Necker-Enfants Malades, Sorbonne Paris Cité, 75015 Paris, France.
authors.forename: Danielle
authors.initials: D
authors.lastname: Canioni
authors.affiliation: Membrane Dynamics and Mechanics of Intracellular Signaling Laboratory, Institut Curie-Centre de Recherche, PSL Research University, 75005 Paris, France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Sengmanivong
authors.affiliation: Cell Adhesion and Mechanics, Institut Jacques Monod, CNRS UMR7592, Paris Diderot University, 75205 Paris, France.
authors.forename: Adeline
authors.initials: A
authors.lastname: Mayeux
authors.affiliation: Institut de Génétique et Développement de Rennes, CNRS UMR6290, 35000 Rennes, France.
authors.forename: Grégoire
authors.initials: G
authors.lastname: Michaux
authors.affiliation: Department of Paediatric Gastroenterology, Hôpital Necker-Enfants Malades, Sorbonne Paris Cité, 75015 Paris, France.|Laboratoire de Microbiologie EA 4065, Faculté de Pharmacie, Université Paris Descartes, 75005 Paris, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Campeotto
authors.affiliation: Department of Pediatric Nutrition and Gastroenterology, Armand-Trousseau Hospital, Assistance Publique-Hôpitaux de Paris, Institute of Cardiometabolism and Nutrition, Pierre et Marie Curie University, 75012 Paris, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Lemale
authors.affiliation: Department of Pediatric Gastroenterology, Assistance Publique-Hôpitaux de Paris, Robert Debré Hospital, Université Paris Diderot, Sorbonne Paris Cité, UMR843, 75019 Paris, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Viala
authors.affiliation: Morphogenesis, Homoeostasis and Pathologies, Institut Jacques Monod, CNRS UMR7592, Paris Diderot University, 75013 Paris, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Poirier
authors.affiliation: Cellular Spatial Organization, Institut Jacques Monod, CNRS UMR7592, Paris Diderot University, 75205 Paris, France.
authors.forename: Nicolas
authors.identifier: 0000-0002-5543-7950
authors.initials: N
authors.lastname: Minc
authors.affiliation: Department of Paediatric Gastroenterology, Hôpital Necker-Enfants Malades, Sorbonne Paris Cité, 75015 Paris, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Schmitz
authors.affiliation: Department of Paediatric Anatomo-Pathology, Hôpital Necker-Enfants Malades, Sorbonne Paris Cité, 75015 Paris, France.
authors.forename: Nicole
authors.initials: N
authors.lastname: Brousse
authors.affiliation: Cell Adhesion and Mechanics, Institut Jacques Monod, CNRS UMR7592, Paris Diderot University, 75205 Paris, France.|Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore.
authors.forename: Benoit
authors.initials: B
authors.lastname: Ladoux
authors.affiliation: Department of Paediatric Gastroenterology, Hôpital Necker-Enfants Malades, Sorbonne Paris Cité, 75015 Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Goulet
authors.affiliation: Cell Adhesion and Mechanics, Institut Jacques Monod, CNRS UMR7592, Paris Diderot University, 75205 Paris, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Delacour
mesh_terms: D000205:Actomyosin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000293:Adolescent; D001696:Biomechanical Phenomena; D018938:Caco-2 Cells; D016764:Cell Polarity; D002648:Child; D002675:Child, Preschool; D003968:Diarrhea, Infantile / Q000235:genetics / Q000378:metabolism; D020895:Enterocytes / Q000737:chemistry / Q000378:metabolism; D000071858:Epithelial Cell Adhesion Molecule / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000737:chemistry* / Q000166:cytology / Q000378:metabolism; D004848:Epithelium / Q000737:chemistry* / Q000378:metabolism; D005260:Female; D006801:Humans; D007223:Infant; D008286:Malabsorption Syndromes / Q000235:genetics / Q000378:metabolism; D008297:Male; D019108:Tight Junctions / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D000205:Actomyosin