Biology subjects

Delacour, D.

Publications and source records attributed to Delacour, D..

5 recordsLinked to original sources

bioRxiv2026

A non-invasive approach for understanding localized force generation in 3D tissues

The development, maintenance and repair of epithelial tissues critically rely on adhesion complexes that ensure structural integrity while enabling dynamic remodeling. Such tissue remodeling underpins both physiological morphogenesis and pathological transformation. Central to these processes are mechanical forces, which tightly couple cytoskeletal organization to adhesion dynamics. Despite extensive investigations in two-dimensional (2D) systems, how these interactions are orchestrated within polarized three-dimensional (3D) epithelia remains largely unresolved. Here, we introduce a new, non-invasive strategy to probe localized force generation within 3D epithelial tissues. We engineered elastic polyacrylamide (PAAm) microbeads with cell-mimetic size and mechanical properties, enabling their seamless integration. In contrast to conventional bead injection approaches, these PAAm microbeads were spontaneously engulfed by the tissue, thereby establishing an intrinsic interface through which bead deformation can be directly correlated with local cytoskeletal architecture and adhesion organization, as visualized through high-resolution imaging combined with quantitative 3D computational reconstruction. Using this approach, we demonstrated that localized mechanical perturbations trigger pronounced cytoskeletal remodelling while preserving global tissue polarity. We further identified the extracellular matrix composition as key determinant of bead-tissue interactions, with collagen-I coating promoting robust adhesion and efficient incorporation. At the bead-cell interface, cells assembled tension-bearing focal adhesions and organized actin stress fibers, revealing the emergence of active cortical stress. Strikingly, quantitative analysis of bead deformation revealed a previously unrecognized mechanical duality: spatially segregated regions of pulling and pushing forces coexisted at the microscale, directly correlated with local cytoskeleton dynamics. This finding challenges the prevailing view of homogenous force application and instead supports a model in which cells deploy highly coordinated and spatially patterned force-generating strategies. Altogether, this integrative and non-invasive strategy offers a comprehensive pipeline for dissecting the dynamic interplay between cellular processes and tissue mechanics during morphogenesis in 3D model systems.

cell 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↗

bioRxiv2022

V0-ATPase downregulation induces MVID-like brush border defects independently of apical trafficking in the mammalian intestine

SummaryIntestinal microvillus atrophy is a major cause of enteropathies such as idiopathic or congenital diarrhea that are often associated with severe morbidity. It can be caused by genetic disorders, inflammatory diseases, toxins or pathogens. In particular, Microvillus inclusion disease (MVID) is characterized by a chronic intractable diarrhea and a severe microvillus atrophy. It is triggered by mutations in MYO5B, STX3, MUNC18.2 or UNC45A which alter epithelial polarity by affecting apical trafficking in intestinal epithelial cells. Furthermore, we recently established that the depletion of the V0 sector of the V-ATPase complex induces an MVID-like phenotype in C. elegans. In this study we investigated the function of the V0-ATPase complex in mouse intestinal organoids. We found that its depletion also triggers a very severe microvillus atrophy in this model. Furthermore, we established that the polarity of intestinal cells is affected in a patient carrying mutations in TCIRG1 which encodes a V0-ATPase subunit. However, V0- ATPase depletion does not recapitulate other MVID-specific phenotypes such as subapical vesicle accumulation and Rab11+ endosomes mislocalization. Finally, we found that the apical localization of the V0-ATPase is disrupted in MVID patients. Altogether these results suggest a role for the V0-ATPase in microvillus atrophy which might be independent from apical trafficking.

cell biology↗

bioRxiv2022

Length-limitation of astral microtubules orients cell divisions in intestinal crypts

Planar spindle orientation is critical for epithelial tissue organization, and generally instructed from the long cell shape axis or cortical polarity domains. We introduced mouse intestinal organoid crypts to study spindle orientation in a monolayered mammalian epithelium. Although spindles were planar in this tissue, mitotic cells remained elongated along the apico-basal axis and polarity complexes were segregated to basal poles, so that spindles oriented in an unconventional manner, orthogonal to both polarity and geometric cues. Using high-resolution 3D imaging, simulations, cell shape and cytoskeleton manipulations, we show that planar divisions resulted from a length-limitation in mitotic-phase astral microtubules which precludes them from interacting with basal polarity, and oriented spindles from the local geometry of apical domains. Accordingly, lengthening microtubules affected spindle planarity, cell positioning and crypt arrangement. We conclude that microtubule length regulation may serve as a key mechanism for spindles to sense local cell shapes and tissue forces to preserve mammalian epithelial architecture.

developmental biology↗

bioRxiv2020

Endosomal spatio-temporal modulation of the cortical RhoA zone conditions epithelial cell organization

At the basis of cell shape and behavior, actomyosin organization and force-generating property are widely studied, however very little is known about the regulation of the contractile network in space and time. Here we study the role of the epithelial-specific protein EpCAM, a contractility modulator, in cell shape and motility, and we show that it is required for the maturation of stress fibers and frontrear polarity acquisition at the single cell level. There, EpCAM ensures the remodeling of a transient active RhoA zone in the cortex of spreading epithelial cells. GTP-RhoA follows the endosomal pathway mediated by Rab35 and EHD1, where it co-evolves together with EpCAM. In fact, EpCAM balances GTP-RhoA turnover in order to tune actomyosin remodeling for cell shape, polarity and mechanical property acquisition. Impairment of GTP-RhoA endosomal trafficking either by EpCAM silencing or Rab35 / EHD1 mutant expression prevents correct myosin-II activity, stress fiber formation, and ultimately cell polarization. Collectively, this work shows that the coupling of EpCAM/RhoA co-trafficking to actomyosin rearrangement is critical for spreading, and advances our understanding of how biochemical and mechanical properties can be coupled for cell plasticity.

cell biology↗