Biology subjects

Villedieu, A.

Publications and source records attributed to Villedieu, A..

7 recordsLinked to original sources

bioRxiv2026

Tissue mechanics sets developmental scaling of collective cell migration

Despite substantial variation in adult size, animals within a species maintain consistent tissue patterns and shapes, a core property known as developmental scaling or size invariance. Developmental scaling has predominantly been attributed to the scaling of morphogen gradients and gene patterns to maintain positional information and cell fate specification1,2. However, development also necessitates collective cell flows that reshape tissues and reposition cells3,4. How these flows adapt to body size remains unclear. By combining quantitative live imaging, experimental perturbations, and physical modeling in the Drosophila thorax epithelium, we address this question in the context of a fundamental process: collective cell migration. We find that migration velocity scales linearly with tissue size, accounting for size-invariant cell positioning. While gene patterning scales with tissue size and modulates force generation, it is not sufficient to ensure proper velocity scaling. Instead, tissue mechanical properties govern the dependence of migration velocity on tissue size, enabling developmental scaling within the physiological range of animal sizes. These findings uncover principles and limits of size invariance by revealing how tissue mechanics sets the scaling behavior of collective cell flows with organismal size.

developmental biology↗

bioRxiv2025

Actin and myosin dynamics during epithelial remodeling in avian gastrulation

Epithelial remodeling is powered by contractile forces exerted by the actomyosin cytoskeleton. In invertebrates, pulsatile contractile flows of the medio-apical actomyosin cortex have been shown to be critical in promoting junction contraction that ultimately drive cell rearrangements, apical constriction, and cell extrusion. However, how actomyosin dynamics drives epithelial remodeling in amniotes remains poorly understood. In this study, we generated transgenic quail lines reporting actin and myosin and investigate their dynamics in gastrulating embryos. We show that during this process, epithelial remodeling events are closely associated with the contraction of junctional myosin. Although we observe medio-apical contractile flows, those appear to contribute to junction contraction by promoting junctional myosin recruitment. Notably, by characterizing live and apoptotic cell extrusions and their associated actomyosin dynamics, we provide new insights into the cellular processes underlying primitive streak formation and the emergence of germ layers.

developmental biology↗

bioRxiv2025

Live imaging and functional characterization of the avian hypoblast redefine the mechanisms of primitive streak induction

In birds and mammals, the formation of the primitive streak, the hallmark of the primary axis and site of gastrulation, is thought to occur when an anterior displacement of the hypoblast (visceral endoderm in mice) lifts its inhibition on the posterior epiblast, enabling the activation of NODAL signaling. Although the anterior movement of the murine visceral endoderm is well documented, the dynamics of the avian hypoblast remain poorly understood. Here, using live imaging and quantitative image analysis, we find that the hypoblast is mechanically coupled to the epiblast and does not migrate away from its posterior end. Instead, the hypoblast moves and deforms passively, in response to the forces transmitted from the epiblast that shape the primitive streak, after its induction. Furthermore, we show that the posterior hypoblast does not exert an inhibitory effect on the epiblast but instead expresses NODAL, which activates primitive streak formation. NODAL concomitantly regulates gene expression in the hypoblast, patterning it along the anteroposterior axis. Our results thus redefine how the primary axis is established in avians, demonstrating that the displacement of the hypoblast and its concomitant anteroposterior patterning are consequences -- rather than drivers -- of primitive streak induction, downstream of NODAL signaling. Essential summaryNODAL asymmetric expression in the hypoblast activates primitive streak formation in the avian embryo.

developmental biology↗

bioRxiv2024

A tension-induced morphological transition shapes the avian extra-embryonic territory

The segregation of the extra-embryonic lineage is one of the earliest events and a key step in amniote development. Whereas the regulation of extra-embryonic cell fate specification has been extensively studied, little is known about the morphogenetic events underlying the formation of this lineage. Here, taking advantage of the amenability of avian embryos to live and quantitative imaging, we investigate the cell- and tissue-scale dynamics of epiboly, the process during which the epiblast expands to engulf the entire yolk. We show that tension arising from the outward migration of the epiblast border on the vitelline membrane stretches extra-embryonic cells, which reversibly transition from a columnar to squamous morphology. The propagation of this tension is strongly attenuated in the embryonic territory, which concomitantly undergoes fluid-like motion, culminating in the formation of the primitive streak. We formulate a simple viscoelastic model in which the tissue responds elastically to isotropic stress but flows in response to shear stress, and show that it recapitulates the flows and deformation of both embryonic and extra-embryonic tissues. Together, our results clarify the mechanical basis of early avian embryogenesis and provide a framework unifying the divergent mechanical behaviors observed in the contiguous embryonic and extra-embryonic territories that make up the epiblast. HighlightsO_LIThe extra-embryonic region expands radially during epiboly C_LIO_LICell area increase accounts for the rapid extra-embryonic expansion C_LIO_LIEpiboly-induced tension reversibly stretches extra-embryonic cells C_LIO_LIA simple viscoelastic model recovers the morphogenesis of the entire epiblast C_LI

developmental biology↗

bioRxiv2022

Homeotic compartment curvature and tension control spatiotemporal folding dynamics.

Shape is a conspicuous and fundamental property of biological systems entailing the function of organs and tissues. While much emphasis has been put on how tissue tension and mechanical properties drive shape changes, whether and how a given tissue geometry influences subsequent morphogenesis remains poorly characterized. Here, we explored how curvature, a key descriptor of tissue geometry, impinges on the dynamics of epithelial tissue invagination. We found that the morphogenesis of the fold separating the adult Drosophila head and thorax segments is driven by the invagination of the Deformed (Dfd) homeotic compartment. Dfd controls invagination by modulating actomyosin organization and in-plane epithelial tension via the Tollo and Dystroglycan receptors. By experimentally introducing curvature heterogeneity within the homeotic compartment, we established that a curved tissue geometry converts the Dfd-dependent in-plane tension into an inward force driving folding. Accordingly, the interplay between in-plane tension and tissue curvature quantitatively explains the spatiotemporal folding dynamics. Collectively, our work highlights how genetic patterning and tissue geometry provide a simple design principle driving folding morphogenesis during development.

developmental biology↗

bioRxiv2021

Topography-induced large-scale anti-parallel collective migration in vascular endothelium

Collective migration of vascular endothelial cells is central for embryonic development, angiogenesis, and wound closure. Although physical confinement of cell assemblies has been shown to elicit specific patterns of collective movement in various cell types, endothelial migration in vivo often occurs without confinement. Here we show that unconfined endothelial cell monolayers on microgrooved substrates that mimic the anisotropic organization of the extracellular matrix exhibit a new type of collective movement that takes the form of a periodic pattern of anti-parallel cell streams. We further establish that the development of these streams requires intact cell-cell junctions and that stream sizes are particularly sensitive to groove depth. Finally, we show that modeling the endothelial cell sheet as an active fluid with the microgrooves acting as constraints on cell orientation predicts the occurrence of the periodic anti-parallel cell streams as well as their lengths and widths. We posit that in unconfined cell assemblies, physical factors that constrain or bias cellular orientation such as anisotropic extracellular matrix cues or directed flow-derived shear forces dictate the pattern of collective cell movement.

biophysics↗

bioRxiv2021

Multi-view confocal microscopy enables multiple organ and whole organism live-imaging

Understanding how development is coordinated in multiple tissues and gives rise to fully functional organs or whole organisms necessitates microscopy tools. Over the last decade numerous advances have been made in live-imaging, enabling high resolution imaging of whole organisms at cellular resolution. Yet, these advances mainly rely on mounting the specimen in agarose or aqueous solutions, precluding imaging of organisms whose oxygen uptake depends on ventilation. Here, we implemented a multi-view multi-scale microscopy strategy based on confocal spinning disk microscopy, called Multi-View confocal microScopy (MuViScopy). MuViScopy enables live-imaging of multiple organs with cellular resolution using sample rotation and confocal imaging without the need of sample embedding. We illustrate the capacity of MuViScopy by live-imaging Drosophila melanogaster pupal development throughout metamorphosis, highlighting how internal organs are formed and multiple organ development is coordinated. We foresee that MuViScopy will open the path to better understand developmental processes at the whole organism scale in living systems that necessitates gas exchange by ventilation.

developmental biology↗