January 2017: When perturbation of the cell contractility triggers an intestinal rare disease

Different teams of the IJM, coordinated by Delphine Delacour in collaboration with clinicians of the Necker Hospital (Paris), showed that the abnormal contractility of epithelial cells would lead to an intestinal rare disease. This study that demonstrates the impact of the tissue geometry in intestinal epithelium maintenance, will be published the 13th of January in Nature Communications.

The Congential Tufting Enteropathy (CTE), alternatively named Intestinal Epithelial Dysplasia, is a rare human congenital enteropathy. It leads to intestinal insufficiency soon after birth and is responsible for chronic diarrhea, persistent during digestive rest and exacerbated by food uptake. No curative treatment is available and the pathology is rapidly lethal unless palliative care (parenteral nutrition). In 73% of the CTE patients, the disease has been associated with pathogenic loss of function mutations of the EPCAM gene coding for an epithelial cell adhesion molecule. The CTE intestinal epithelium displays unique morphological abnormalities, materialized by formation of aberrant focal stacks of pseudo-multilayered enterocytes on the villus, named “tufts”.

Inside the Benoit Ladoux and René-Marc’s lab « Cell Adhesion and Mechanics », Delphine Delacour in collaboration with the Paediatric Gastroenterology Department of Necker Hospital, characterised the CTE epithelium by using cell biology and biophysics approaches. To understand the origins of the disease at the tissue level, they set up a cell culture system that mimics the intestinal epithelium geometry in vitro. They show that EpCAM loss provokes unusual cell polarity defects and a strong perturbation of the intestinal tissue along the villus. These abnormalities stem from an inappropriate actomyosin activity at tricellular contacts. They conclude that the homeostasis of the actomyosin apparatus is crucial for the maintenance of individual epithelial cell polarity, but also for the integrity of an epithelial monolayer in physical tissue constraints. Since cellular defects and tissue-scale changes are reversible under cell contractility inhibition, this study may open new therapeutic perspectives for CTE patients.

To find out more:
Contractile forces at tricellular contacts modulate epithelial organization and monolayer integrity. Salomon J, Gaston C, Magescas J, Duvauchelle B, Canioni D, Sengmanivong L, Mayeux A, Michaux G, Campeotto F, Lemale J, Viala J, Poirier F, Minc N, Schmitz J, Brousse N, Ladoux B, Goulet O, Delacour D. Nature Communications

Contact: Delphine Delacour, group Cell Adhesion and Mechanics tél.: + 33 (0)1 57 27 80 67

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