As forças contrácteis nos contatos tricelulares modulam a organização epitelial e a integridade da monocamada: mero acaso, fortuita necessidade ou design inteligente?

Contractile forces at tricellular contacts modulate epithelial organization and monolayer integrity

Julie Salomon, Cécile Gaston, Jérémy Magescas, Boris Duvauchelle, Danielle Canioni, Lucie Sengmanivong, Adeline Mayeux, Grégoire Michaux, Florence Campeotto, Julie Lemale, Jérôme Viala, Françoise Poirier, Nicolas Minc, Jacques Schmitz, Nicole Brousse, Benoit Ladoux, Olivier Goulet & Delphine Delacour

Nature Communications 8, Article number: 13998 (2017)

doi: 10.1038/ncomms13998  

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Cell adhesion Mechanisms of disease

Received: 10 October 2016 Accepted: 17 November 2016

Published online: 13 January 2017

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.

Acknowledgements

We thank Patrick Tounian from the Armand Trousseau Hospital paediatric gastroenterology department (Paris, France), Marc Bellaïche and Jean-Pierre Hugot from the Robert Debré Hospital paediatric gastroenterology department (Paris, France) for contributing to the CTE biopsy collection. We thank the CTE patients and their family, for allowing us to study biopsies. We thank Sylvie Robine, René-Marc Mège, Maud Dumoux and Anne-Lise Haenni for critical reading of the manuscript. We thank Gianluca Grenci and Mohammed Ashraf (Microfabrication facility, Mechanobiology Institute (MBI), National University of Singapore (NUS), Singapore) for the design and generation of silicon wafers. We thank Léo Veyrier, Thomas Eche, Vincent Leguillier and Victoria Djordjevic for technical help. We thank Sandra Colas and Vanessa Lory for their expertise (Unité de Recherche Clinique (URC), Necker Hospital, Paris, France). We thank Virginie Bazin from the Electron Microscopy facility of the Institut de Biologie Paris-Seine (IBPS, Paris) for the SEM sample preparation and technical assistance during acquisitions. We thank François Waharte from the Nikon centre imaging facility (Curie Institute, Paris). We thank Rémi Le Borgne (ImagoSeine) for cell monolayer sample preparation for transmission electron microscopy. Confocal microscopy analyses were performed in the ImagoSeine microscopy facility (Institut Jacques Monod, IJM). High-resolution 3D-SIM and SP8 confocal analyses were acquired in the Nikon centre imaging facility (Curie Institute, Paris). This work was supported by grants from the GEFLUC Paris-Ile de France ‘Les entreprises contre le cancer’, from the ‘Fondation pour la Recherche Médicale’, from the ‘Association pour la Recherche contre le Cancer’, from ‘La Ligue, Comité de Paris’, ‘Initiatives d’excellence’ (Idex ANR-11-IDEX-0005-02)—Labex «Who Am I?» (ANR-11-LABX-0071) and from the ‘Assistance Publique—Hôpitaux de Paris, AP-HP’ (Projets Hospitaliers de Recherche Clinique (PHRC) grants).

Author information

Author notes

Julie Salomon, Cécile Gaston & Jérémy Magescas

These authors contributed equally to this work

Affiliations

Cell Adhesion and Mechanics, Institut Jacques Monod, CNRS UMR7592, Paris Diderot University, 75205 Paris, France

Julie Salomon, Cécile Gaston, Jérémy Magescas, Adeline Mayeux, Benoit Ladoux & Delphine Delacour

Department of Paediatric Gastroenterology, Hôpital Necker-Enfants Malades, Sorbonne Paris Cité, 75015 Paris, France

Julie Salomon, Florence Campeotto, Jacques Schmitz & Olivier Goulet

Morphogenesis, Homoeostasis and Pathologies, Institut Jacques Monod, CNRS UMR7592, Paris Diderot University, 75013 Paris, France

Boris Duvauchelle & Françoise Poirier

Department of Paediatric Anatomo-Pathology, Hôpital Necker-Enfants Malades, Sorbonne Paris Cité, 75015 Paris, France

Danielle Canioni & Nicole Brousse

Membrane Dynamics and Mechanics of Intracellular Signaling Laboratory, Institut Curie–Centre de Recherche, PSL Research University, 75005 Paris, France

Lucie Sengmanivong

Institut de Génétique et Développement de Rennes, CNRS UMR6290, 35000 Rennes, France

Grégoire Michaux

Laboratoire de Microbiologie EA 4065, Faculté de Pharmacie, Université Paris Descartes, 75005 Paris, France

Florence Campeotto

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

Julie Lemale

Department of Pediatric Gastroenterology, Assistance Publique-Hôpitaux de Paris, Robert Debré Hospital, Université Paris Diderot, Sorbonne Paris Cité, UMR843, 75019 Paris, France

Jérôme Viala

Cellular Spatial Organization, Institut Jacques Monod, CNRS UMR7592, Paris Diderot University, 75205 Paris, France

Nicolas Minc

Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore

Benoit Ladoux

Contributions

J.S., C.G., J.M., B.D., A.M., L.S., G.M., B.L. and D.D. performed the experiments. D.C., F.C., J.L., J.V., N.B. and O.G. provided patient biopsies. F.P., J.S., N.B. and O.G. participated in interpretation of the experiments and discussion. J.S., C.G., J.M., N.M., B.L. and D.D. designed the experiments. J.S., C.G., J.M. and D.D. performed analyses. J.S. and D.D. coordinated the overall research and experiments, and wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Delphine Delacour.

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