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Nat Commun. 2017 Jan 13;8:13998. doi: 10.1038/ncomms13998.

Contractile forces at tricellular contacts modulate epithelial organization and monolayer integrity.

Author information

1
Cell Adhesion and Mechanics, Institut Jacques Monod, CNRS UMR7592, Paris Diderot University, 75205 Paris, France.
2
Department of Paediatric Gastroenterology, Hôpital Necker-Enfants Malades, Sorbonne Paris Cité, 75015 Paris, France.
3
Morphogenesis, Homoeostasis and Pathologies, Institut Jacques Monod, CNRS UMR7592, Paris Diderot University, 75013 Paris, France.
4
Department of Paediatric Anatomo-Pathology, Hôpital Necker-Enfants Malades, Sorbonne Paris Cité, 75015 Paris, France.
5
Membrane Dynamics and Mechanics of Intracellular Signaling Laboratory, Institut Curie-Centre de Recherche, PSL Research University, 75005 Paris, France.
6
Institut de Génétique et Développement de Rennes, CNRS UMR6290, 35000 Rennes, France.
7
Laboratoire de Microbiologie EA 4065, Faculté de Pharmacie, Université Paris Descartes, 75005 Paris, France.
8
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.
9
Department of Pediatric Gastroenterology, Assistance Publique-Hôpitaux de Paris, Robert Debré Hospital, Université Paris Diderot, Sorbonne Paris Cité, UMR843, 75019 Paris, France.
10
Cellular Spatial Organization, Institut Jacques Monod, CNRS UMR7592, Paris Diderot University, 75205 Paris, France.
11
Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore.

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.

PMID:
28084299
PMCID:
PMC5241865
DOI:
10.1038/ncomms13998
[Indexed for MEDLINE]
Free PMC Article

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