Biology subjects

Berrebi, D.

Publications and source records attributed to Berrebi, D..

3 recordsLinked to original sources

bioRxiv2026

EpCAM sustains crypt mechanics and prevents aberrant remodeling

Crypt morphogenesis is a fundamental process that drives intestinal growth and maintains its homeostasis. Although intestinal tissue mechanics is recognized as pivotal for early crypt initiation and budding, the molecular mechanisms that couple epithelial forces to mature crypt behavior remain largely unexplored. In particular, while Paneth cells have been proposed to be implicated in the mechanical control of crypt remodeling and fission, the underlying pathways have remained elusive. Here, we identified EpCAM (Epithelial Cell Adhesion Molecule) as a key regulator of epithelial contractility and crypt morphogenesis. EpCAM was preferentially enriched at lateral interfaces of Paneth cells in vivo and in organoid models, where it maintained cortical tension and contractile organization. Loss of EpCAM disrupted crypt cell cortical myosin II-A localization, leading to aberrant Paneth cell apical contractility, enlarged apical surfaces, distorted pyramidal morphology, and altered aspect ratios. Consequently, Paneth cells lose their tight clustering in crypt base, their spatial distribution along the crypt axis becomes irregular, and the collective architecture of the crypt epithelium was compromised. At the tissue level, EpCAM deficiency profoundly perturbed crypt fission, increasing fission frequency while favoring asymmetric outcome both in EPCAM-mutated Congenital Tufting Enteropathy (CTE) patients. Live imaging of EpCAM-knockout mouse organoids confirmed a failure in the spatial control of crypt bifurcation. Collectively, our findings revealed that EpCAM is not required to initiate fission, but is essential to coordinate the mechanical forces and ensure correct division of the crypt. We showed that EpCAM-dependent biomechanical integrity of Paneth cells generates a stabilizing force field at the crypt base, orchestrating coordinated tissue remodeling. Disruption of this program led to unbalanced force transmission, distorted crypt geometry, and aberrant fission outcomes, revealing a critical link between epithelial mechanics and intestinal morphogenesis.

developmental biology↗

bioRxiv2024

A multicellular actin star network underpins epithelial organization and connectivity

Epithelial tissues serve as physical barriers against various external pressures yet remarkably maintain structural stability. Various cellular apparatus including bicellular junction and actomyosin network contribute to the epithelial integrity, packing and remodelling. Although their role in morphogenetic and mechanical processes have been extensively studied during embryogenesis and disease development, their synergistic effects in maintaining tissue organization and connection remain poorly understood. In this study, we discovered a tissue-scale actomyosin network connected through bicellular junctions and manifested in the villi of adult murine intestinal tissue. Later we reproduced such supracellular structure in the differentiated compartment of ex vivo intestinal epithelium model. The self-organized actomyosin networks comprised individual actin nodes in each hexagonal cell at the epithelial base with six radial actin branches, presenting an actin star unit. The repeated units were connected through the bicellular junctions, forming a large, multicellular array covering the differentiated domains. Functionally, actin stars contribute to epithelial morphological stability by maintaining cell hexagonality and packing, thereby preserving the solid-like order of the epithelium. Laser ablation experiments validate a modified vertex theoretical model that connects the emergence of such solid-like order to the onset of tension along the actin star branches. Actin stars also acted as locks at the basal side minimizing protrusive activity in the epithelial layer, hindering cell migration and disorganization of the epithelial tissue. Altogether, the supracellular actin star network constitutes a basal biomechanical apparatus coordinating epithelial tissue stability and organization.

cell biology↗

bioRxiv2019

Nod2 protects remote small intestinal sites in case of colonic inflammation.

NOD2 mutations are key risk factors for Crohns disease (CD). NOD2 contributes to intestinal homeostasis by regulating innate and adaptive immunity together with intestinal epithelial function. However, the roles of NOD2 during gut inflammation is not known. We initially observed that NOD2 expression was increased in epithelial cells remote from inflamed areas in CD patients. To explore this finding, Nod2 mRNA expression, inflammation and gut permeability were examined in the small bowel of wild-type (WT), Nod2 knockout and Nod2 mutant mice after rectal instillation of 2,4,6-trinitrobenzene sulfonic acid (TNBS). In WT mice, Nod2 upregulation remote to rectal injury was associated with pro-inflammatory cytokine expression, recirculating CD4+ T-cells, increased paracellular permeability and myosin like chain kinase activity. Nod2 knockout or mutation led to duodenitis and ileitis demonstrating the remote protective role of Nod2. Bone morrow stem cell (BMSC) transplantations indicated that the small intestinal inflammation was due to NOD2 loss in both hematopoietic and non-hematopoietic compartments. As a whole, WT but not mutant NOD2 prevents disease extension at sites remote from the initial intestinal injury.

immunology↗