Biology subjects

Marcq, P.

Publications and source records attributed to Marcq, P..

7 recordsLinked to original sources

bioRxiv2025

Wnt signaling modulates tissue mechanics, actin order, and regeneration in Hydra vulgaris

Hydra vulgaris is a powerful model organism in the study of axial patterning and regeneration. While recent models emphasize the importance of mechanical cues in establishing the body axis of Hydra tissue spheres, the precise role of the Wnt pathway, known to be central to axial patterning, in regulating tissue mechanics and cytoskeletal organization remains unclear. In this paper, we pharmacologically modulated the canonical Wnt pathway using Alsterpaullone and iCRT14 and assessed their effects on regeneration, tissue rheology, osmotic oscillations and actin organization in Hydra tissue spheres. We found that Wnt activation prevents full regeneration, softens the constitutive tissues, disrupts osmotic oscillations, leads to an accumulation of dense actin filaments but impairs their orientational order. Conversely, we found that Wnt inhibition partially impairs regeneration and reduces actin filament presence while preserving alignment. These results support the underlying hypotheses of two existing mechano-chemical models of Hydra patterning, suggesting that Wnt-driven feedbacks on both tissue stiffness and actin order could contribute to the robust emergence of body axes. Our findings highlight the possibility of redundant and coupled mechanisms in the Hydra patterning system, potentially explaining its robustness.

biophysics↗

bioRxiv2023

Mechanical characterization of regenerating Hydra tissue spheres

Hydra vulgaris, long known for its remarkable regenerative capabilities, is also a longstanding source of inspiration for models of spontaneous patterning. Recently, it became clear that early patterning during Hydra regeneration is an integrated mechano-chemical process where morphogen dynamics is influenced by tissue mechanics. One roadblock to understand Hydra self-organization is our lack of knowledge about the mechanical properties of these organisms. In this paper, we combined microfluidic developments to perform parallelized microaspiration rheological experiments and numerical simulations to characterize these mechanical properties. We found three different behaviors depending on the applied stresses: an elastic response, a visco-elastic one and tissue rupture. Using models of deformable shells, we quantify their Youngs modulus, shear viscosity as well as the critical stresses required to switch between behaviors. Based on these experimental results, we propose a description of the tissue mechanics during normal regeneration. Our results provide a first step towards the development of original mechano-chemical models of patterning grounded in quantitative, experimental data. Statement of significanceHydra vulgaris is a remarkable organism thanks to its regenerative abilities. One can cut this animal into several pieces which will reform a full Hydra in a few days. In this process, the pieces have to define a new organizing axis. Recently, researchers have shown that this axis definition is under mechanical control. One roadblock to understand the relationship between tissue mechanics and Hydra biology is our lack of knowledge about the mechanical state of this organism. Here, we perform a mechanical characterization using a combination of microaspiration setups and numerical simulations. We finally propose a description of what happens at the mechanical level during Hydra regeneration, allowing quantitative approaches questioning the role of mechanical cues in axis definition.

biophysics↗

bioRxiv2022

Mechanical stress driven by rigidity sensing governs epithelial stability

Epithelia act as a barrier against environmental stress and abrasion and in vivo they are continuously exposed to environments of various mechanical properties. The impact of this environment on epithelial integrity remains elusive. By culturing epithelial cells on 2D hydrogels, we observe a loss of epithelial monolayer integrity through spontaneous hole formation when grown on soft substrates. Substrate stiffness triggers an unanticipated mechanical switch of epithelial monolayers from tensile on soft to compressive on stiff substrates. Through active nematic modelling, we find unique patterns of cell shape texture called nematic topological defects that underpin large isotropic stress fluctuations at certain locations thereby triggering mechanical failure of the monolayer and hole opening. Our results show that substrate stiffness provides feedback on monolayer mechanical state and that topological defects can trigger stochastic mechanical failure, with potential application towards a mechanistic understanding of compromised epithelial integrity in bacterial infection, tumor progression and morphogenesis.

biophysics↗

bioRxiv2021

Enhanced RhoA signaling stabilizes E-cadherin in migrating epithelial monolayers.

Epithelia migrate as physically coherent populations of cells. Earlier studies revealed that mechanical stress accumulates in these cellular layers as they move. These stresses are characteristically tensile in nature and have often been inferred to arise when moving cells pull upon the cell-cell adhesions that hold them together. We now report that epithelial tension at adherens junctions between migrating cells also reflects an increase in RhoA-mediated junctional contractility. We find that active RhoA levels were stimulated by p114 RhoGEF at the junctions between migrating MCF-7 monolayers, and this is accompanied by increased levels of actomyosin and mechanical tension. By applying a strategy to restore active RhoA specifically at adherens junctions by manipulating its scaffold, anillin, we found that this junctional RhoA signal was necessary to stabilize junctional E-cadherin during epithelial migration. We suggest that stabilization of E-cadherin by RhoA serves to increase cell-cell adhesion against the mechanical stresses of migration.

cell biology↗

bioRxiv2019

Emergence of single cell mechanical behavior and polarity within epithelial monolayers drives collective cell migration

The directed migration of cell collectives is essential in various physiological processes, such as epiboly, intestinal epithelial turnover, and convergent extension during morphogenesis as well as during pathological events like wound healing and cancer metastasis1,2. Collective cell migration leads to the emergence of coordinated movements over multiple cells. Our current understanding emphasizes that these movements are mainly driven by large-scale transmission of signals through adherens junctions3,4. In this study, we show that collective movements of epithelial cells can be triggered by polarity signals at the single cell level through the establishment of coordinated lamellipodial protrusions. We designed a minimalistic model system to generate one-dimensional epithelial trains confined in ring shaped patterns that recapitulate rotational movements observed in vitro in cellular monolayers and in vivo in genitalia or follicular cell rotation5-7. Using our system, we demonstrated that cells follow coordinated rotational movements after the establishment of directed Rac1-dependent polarity over the entire monolayer. Our experimental and numerical approaches show that the maintenance of coordinated migration requires the acquisition of a front-back polarity within each single cell but does not require the maintenance of cell-cell junctions. Taken together, these unexpected findings demonstrate that collective cell dynamics in closed environments as observed in multiple in vitro and in vivo situations5,6,8,9 can arise from single cell behavior through a sustained memory of cell polarity.

biophysics↗

bioRxiv2019

Myosin II isoforms play distinct roles in adherens junction biogenesis

Adherens junction (AJ) assembly under force is essential for many biological processes like epithelial monolayer bending, collective cell migration, cell extrusion and wound healing. The acto-myosin cytoskeleton acts as a major force-generator during the de novo formation and remodelling of AJ. Here, we investigated the role of myosinII isoforms in epithelial junction assembly. Myosin IIA (NMIIA) and Myosin IIB (NMIIB) differentially regulate biogenesis of adherens junction through association with distinct actin networks. Analysis of junction dynamics, actin organization, and mechanical forces of control and knockdown cells for myosins revealed that NMIIA provides the mechanical tugging force necessary for cell-cell junction reinforcement and maintenance. NMIIB is involved in E-cadherin clustering, maintenance of a branched actin layer connecting E-cadherin complexes and perijunctional actin fibres leading to the building-up of anisotropic stress. These data reveal unanticipated complementary functions of NMIIA and NMIIB in the biogenesis and integrity of AJ.

cell biology↗

bioRxiv2018

Sustained oscillations of epithelial cell sheets

Morphological changes during development, tissue repair, and disease largely rely on coordinated cell movements and are controlled by the tissue environment. Epithelial cell sheets are often subjected to large scale deformation during tissue formation. The active mechanical environment in which epithelial cells operate have the ability to promote collective oscillations, but how these cellular movements are generated and relate to collective migration remains unclear. Here, combining in vitro experiments and computational modelling we describe a novel mode of collective oscillations in confined epithelial tissues where the oscillatory motion is the dominant contribution to the cellular movements. We show that epithelial cells exhibit large-scale coherent oscillations when constrained within micro-patterns of varying shapes and sizes, and that their period and amplitude are set by the smallest confinement dimension. Using molecular perturbations, we then demonstrate that force transmission at cell-cell junctions and its coupling to cell polarity are pivotal for the generation of these collective movements. We find that the resulting tissue deformations are sufficient to trigger mechanotransduction within cells, potentially affecting a wide range of cellular processes.

biophysics↗