Biology subjects

Villeneuve, C.

Publications and source records attributed to Villeneuve, C..

8 recordsLinked to original sources

bioRxiv2026

Tissue-scale mechanics controls differentiation strategy and dynamics of epithelial multilayering

Generating and maintaining multilayered epithelia requires coordinated cell division, differentiation, and tissue architecture, yet the precise mechanisms of multilayering remain unclear. Using the developing mouse epidermis, we show that basal stem cells adopt distinct multilayering strategies depending on tissue mechanics. Combining quantitative morphometry, embryo live imaging and physical modeling, we observe that early in development, the epidermis is fluid-like, allowing undifferentiated cells to move suprabasally through perpendicular divisions or basal detachment before differentiating. As the tissue matures and rigidifies, a mechanical barrier is established that only allows upward movement of basal cells that have committed to differentiation. The final step of this commitment is delamination that requires Notch signaling, triggered by increased tissue stiffness and jamming. This mechanical regulation orchestrates a feedback loop that induces cell upward motion precisely when the basal layer becomes crowded. Together, our findings identify tissue mechanics as the key determinant of how tissues drive multilayering and reveal mechanically regulated Notch signaling as a driver of epidermal delamination.

cell biology↗

bioRxiv2025

Predicting space use patterns of a territorial top predator: from individual movement decisions to Arctic fox space use

O_LIPredicting animal space use could greatly improve our understanding and forecasting of ecological processes. Despite growing interest, the development of predictive space use models amenable to the integration of spatial processes into ecological frameworks have yet to reach their full potential. C_LIO_LIUsing high-resolution tracking data collected at 4-minute intervals from 26 Arctic foxes over five years, we developed a predictive space use model based on a step-selection approach. We assessed fine-scale habitat selection in relation to prey distribution, landscape features, and ecological constraints such as central place foraging and territoriality. We then used these results to build an agent-based model simulating fox space use and evaluated its ability to reproduce observed space use patterns. C_LIO_LIStep-selection analyses confirmed that fox movements were driven by habitat type, goose nest density, distance to den, and avoidance of distance to the home range boundary. Agent-based simulations closely matched empirical tracking data and accurately forecasted fox space use, even for individuals excluded from model parameterization. C_LIO_LIBy developing a predictive model of predator space-use, our study provides a foundation for incorporating additional components of the predation sequence and contributes to more spatially informed approaches in predator-prey ecology. C_LI

ecology↗

bioRxiv2025

Fibroblast depletion reveals mammalian epithelial resilience across neonatal and adult stages

Regenerative organs, like the skin, depend on niche-stem cell interactions that sustain continuous cellular turnover. In cell culture, skin fibroblasts promote epidermal stem cell proliferation and differentiation. Yet, it remains elusive how fibroblasts regulate epidermal stem cell behaviors and differentiation in skin in vivo. Here, we asked how fibroblast depletion may impact epidermal stem cell proliferation in the context of adult homeostasis. Surprisingly, we find that significant depletion of fibroblast density does not affect epidermal stem cell proliferative capacity during adult stages in vivo. We next probed earlier neonatal stages when skin is actively remodeling but found no change in epidermal stem cell proliferative capacity following fibroblast depletion. These results demonstrate that across different ages, epidermal stem cell proliferative capacity can persist in the face of a largely reduced fibroblast population. Interestingly, neonatal fibroblast depletion does not significantly reduce their secreted collagen I density but affects basement membrane mechanics and epidermal stem cell delamination. Despite these changes, the skin continues to maintain its protective barrier function. Thus, our work demonstrates the skin regenerative program employs robust compensatory mechanisms in the face of fibroblast depletion to maintain functional capacity.

cell biology↗

bioRxiv2025

Transformation of Petri net models of biological signaling networks into influence graphs

A common depiction for biological signaling networks is the influence graph in which the activation and inhibition effects between molecular species are shown with vertices and arcs connecting them. Another formalism for reaction-based models is the Petri nets which has a graphical representation and a mathematical notation that enables structural analysis and quantitative simulation. In this paper, we present an algorithm based on Petri nets topological features for the transformation of the computational model of a biological signaling network into an annotated influence graph. We also show the transformation of the Petri nets model of the beta-adrenergic receptor activating the PKA-MAPK signaling network into its representation as an influence graph.

bioinformatics↗

bioRxiv2024

Piezo1 balances membrane tension and cortical contractility to stabilize intercellular junctions and maintain epithelial barrier integrity

Formation of a bi-directional skin barrier is essential for organismal survival and maintenance of tissue homeostasis. Barrier formation requires positioning of functional tight junctions (TJ) to the most suprabasal viable layer of the epidermis through a mechanical circuit that is driven by generation of high tension at adherens junctions. However, what allows the sensing of tension build-up at these adhesions and how this tension is balanced to match the requirements of tissue mechanical properties is unclear. Here we show that the mechanosensitive ion channel Piezo1 is essential for the maturation of intercellular junctions into functional, continuous adhesions. Deletion of Piezo1 results in an imbalance of cell contractility and membrane tension, leading to a delay in adhesion maturation. Consequently, the requirement for Piezo1 activity can be bypassed by lowering contractility or elevating membrane tension. In vivo, Piezo1 function in adhesion integrity becomes essential only in aged mice where alterations in tissue mechanics lead to impaired TJs and barrier dysfunction. Collectively these studies reveal an essential function of Piezo1 in the timely establishment and maintenance of cell-cell junctions in the context of a mechanically tensed epidermis.

cell biology↗

bioRxiv2022

Mechanical forces across compartments coordinate cell shape and fate transitions to generate tissue architecture

Morphogenesis and cell state transitions must be coordinated in time and space to produce a functional tissue. An excellent paradigm to understand the coupling of these processes is mammalian hair follicle development, initiated by the formation of an epithelial invagination - termed placode - that coincides with the emergence of a designated hair follicle stem cell population. The mechanisms directing the deformation of the epithelium, cell state transitions, and physical compartmentalization of the placode are unknown. Here, we identify a key role for coordinated mechanical forces stemming from contractile, proliferative, and proteolytic activities across the epithelial and mesenchymal compartments in generating the placode structure. A ring of fibroblast cells gradually wraps around the placode cells to generate centripetal contractile forces, which in collaboration with polarized epithelial myosin activity promote elongation and local tissue thickening. These mechanical stresses further enhance and compartmentalize Sox9 expression to promote stem cell positioning. Subsequently, proteolytic remodeling locally softens the basement membrane to facilitate release of pressure on the placode, enabling localized cell divisions, tissue fluidification, and epithelial invagination into the underlying mesenchyme. Together, our experiments and modeling identify dynamic cell shape transformations and tissue-scale mechanical co-operation as key factors for orchestrating organ formation.

developmental biology↗

bioRxiv2021

A new approach to measure forces at junction vertices in an epithelium

The mechanical properties of cell-cell junctions are critical for the stability of an epithelium. Cell-cell junction ablation experiments are classically used as a readout for junctional mechanics. However, without the knowledge of the viscoelastic properties of the microenvironment of the ablated junction, tensile junctional forces cannot be measured. Here we combine laser ablation with intracellular microrheology and develop a model to measure tensile forces exerted on cell-cell junctions. We show that the overexpression of the proto-oncogene atypical Protein Kinase C iota (aPKCi) in a single cell within a normal epithelium induces a gradient of junctional tension with neighbouring cells. Our method allows us to demonstrate that junctions contacting the aPKCi-overexpressing cell display a mechanical asymmetry which correlates with the levels of E-cadherin and P-MLC2. Measuring intracellular viscoelasticity is crucial for accurate measurements of cell-cell junction mechanics in the context of development or cancer research. TeaserWe combine cytoplasmic and junctional mechanics to detect asymmetry in forces exerted on cell-cell junctions.

cell biology↗

bioRxiv2019

A new analytical pipeline for the study of the onset of mammary gland oncogenesis based on mammary organoid transplantation and organ clearing

Metastasis formation is a multi-step process starting from the dissemination of transformed carcinomatous cells from the primary tumor and could occur at a very early stage of oncogenesis, before primary tumor detection. The adult mammary gland provides a unique model to investigate epithelial cell dissemination processes. Tissue clearing techniques allow imaging samples of large volume. uDSICO clearing, one of the latest tissue clearing technique developed, provides optical imaging of whole organ due to organ clearing and tissue size reduction. We wanted to take advantage of this technique to study rare events occurring in vivo. Here, we have established a new analytical pipeline exploiting the regenerative properties of the mammary epithelium following orthotropic transplantation of organoids together with the uDISCO organ size reduction and clearing method to study early cell dissemination in the mammary gland. As proof of concept, we analyzed the localization of epithelial cells overexpressing the oncogenic protein atypical protein kinase C iota (aPKCi+) in the normal mammary gland and we were able to visualize epithelial aPKCi+ cells, surrounded by normal epithelial cells, escaping from the normal mammary epithelium and disseminating into the surrounding stroma.

cell biology↗