Biology subjects

Graner, F.

Publications and source records attributed to Graner, F..

12 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↗

bioRxiv2026

Three phylogenetic metrics are compatible with natural evolution of the earliest SARS-CoV-2 sequence

Comparative analyses of coronavirus sequences can unravel important aspects of their complex evolution. Here we develop a method to infer past recombination breakpoints based on minimizing homoplasies count. We test it on three outbreak viruses (SARS-CoV-1, MERS-CoV, and SARS-CoV-2) and various chimeric coronaviruses as positive controls. We identify genomic regions evolving under distinct selective pressures. We also trace possible signs of human-made manipulations using metrics such as synonymous and non-synonymous mutation rates, codon usage and insertion patterns. Our pipeline appears to efficiently detect synthetic sequence optimization or genome re-encoding, but does not identify chimeras of natural viruses. Unlike in positive controls, with our method no signal of human-made manipulation is detected in SARS-CoV-1, MERS-CoV, nor SARS-CoV-2.

evolutionary biology↗

bioRxiv2024

Drosophila glue evolved different adhesive and mechanical properties across 50 million years

Drosophila glue, a bioadhesive produced by fly larvae to attach themselves to a substrate for several days, has recently gained attention for its peculiar adhesive and mechanical properties. Although Drosophila glue production was described more than 50 years ago, a general survey of the adhesive and mechanical properties of this proteinaceous gel across Drosophila species is lacking. To measure adhesion, we present here a protocol that is robust to variations in protocol parameters, pupal age and calculation methods. We find that the glue, which covers the entire pupal surface, increases the animal rigidity and plasticity when bound to a glass slide. Our survey of pupal adhesion in 25 Drosophilidae species reveals la wide range of phenotypes, from species that produce no or little glue and adhere little, to species that produce high amounts of glue and adhere strongly. One species, D. hydei, stands out from the rest and emerges as a promising model for the development of future bioadhesives, as it has the highest detachment force per glue area and produces relatively large amounts of glue relative to its size. We also observe that species that invest more in glue tend to live in more windy and less rainy climates, suggesting that differences in pupal adhesion properties across species are shaped by ecological factors. Our present survey provides a basis for future biomimetic studies based on Drosophila glue.

biophysics↗

bioRxiv2023

Apical constriction requires patterned apical surface remodeling to synchronize cellular deformation

Apical constriction is a basic mechanism for epithelial morphogenesis, making columnar cells into wedge shape and bending a flat cell sheet. It has long been thought that an apically localized myosin generates a contractile force and drives the cell deformation. However, when we tested the increased apical surface contractility in a cellular Potts model simulation, the constriction increased pressure inside the cell and pushed its lateral surface outward, making the cells adopt a drop shape instead of the expected wedge shape. To keep the lateral surface straight, we considered an alternative model in which the cell shape was determined by cell membrane elasticity and endocytosis, and the increased pressure is balanced among the cells. The cellular Potts model simulation succeeded in reproducing the apical constriction, and it also suggested that a too strong apical surface tension might prevent the tissue invagination.

developmental biology↗

bioRxiv2023

Apical-driven cell sorting optimised for tissue geometry ensures robust patterning

Tissue patterning coordinates morphogenesis, cell dynamics and fate specification. Understanding how these processes are coupled to achieve precision despite their inherent variability remains a challenge. Here, we investigate how salt-and-pepper epiblast and primitive endoderm (PrE) cells sort and robustly pattern the inner cell mass (ICM) of mammalian blastocysts. Quantifying cellular dynamics and mechanics together with simulations show a key role for the autonomously acquired apical polarity of mouse PrE cells in coupling cell fate and dynamics in tissue contexts. Specifically, apical polarity forms actin protrusions and is required for Rac1-dependent migration towards the ICM surface, where PrE cells are trapped due to decreased tension at their apical domain, while depositing an extracellular matrix gradient, breaking the tissue-level symmetry and collectively guiding their own migration. Tissue size perturbations and comparison with monkey blastocysts further demonstrate that the fixed proportion of PrE/epiblast cells is optimal and robust to variability in embryo size.

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↗

bioRxiv2022

A microfluidic platform to investigate the role of mechanical constraints on tissue reorganization

Mechanical constraints have a high impact on development processes, and there is a need for new tools to investigate the role of mechanosensitive pathways in tissue reorganization during development. We present here experiments where embryonic cell aggregates are aspired through constrictions in microfluidic channels, generating highly heterogeneous flows and high cell deformations that can be imaged using two-photon microscopy. This approach provides a way to measure in situ local viscoelastic properties of 3D tissues and connect them to intracellular and intercellular events such as cell shape changes and cell rearrangements. Perspectives include applications on organoids to investigate and quantify rheological properties of tissues, and to understand how constraints affect development.

biophysics↗

bioRxiv2021

Cell shape anisotropy and motility constrain self-organised feather pattern fidelity in birds

Cellular self-organisation can emerge from stochastic fluctuations in properties of a developing tissue1-3. This mechanism explains the production of various motifs seen in nature4-7. However, events channelling its outcomes such that patterns are produced with reproducible precision key to fitness remain unexplored. Here, we compared the dynamic emergence of feather primordia arrays in poultry, finch, emu, ostrich and penguin embryos and correlated inter-species differences in pattern fidelity to the amplitude of dermal cell anisotropy in the un-patterned tissue. Using live imaging and ex vivo perturbations in these species, we showed that cell anisotropy optimises cell motility for sharp and precisely located primordia formation, and thus, proper pattern geometry. These results evidence a mechanism through which collective cellular properties of a developmental pattern system ensure stability in its self-organisation and contribute to its evolution.

developmental biology↗

bioRxiv2020

Temperature change has the same effect as genetic variation on a morphological trait involved in reproductive isolation between Drosophila sister species

Male genitalia are usually extremely divergent between closely related species, but relatively constant within one species. Here we examine the effect of temperature on the shape of the ventral branches, a male genital structure involved in reproductive isolation, in the sister species Drosophila santomea and D. yakuba. We designed a semi-automatic measurement pipeline that can reliably identify curvatures and landmarks based on manually digitized contours of the ventral branches. With this method, we observed that temperature does not affect ventral branches in D. yakuba but that in D. santomea ventral branches tend to morph into a D. yakuba-like shape at lower temperature. Our results suggest that speciation of D. santomea and D. yakuba was associated with a change in genitalia plasticity.

evolutionary biology↗

bioRxiv2019

From heterogenous morphogenetic fields to homogeneous regions as a step towards understanding complex tissue dynamics

Within developing tissues, cell proliferation, cell motility, and other cell behaviors vary spatially, and this variability gives a complexity to the morphogenesis. Recently, novel formalisms have been developed to quantify tissue deformation and underlying cellular processes. A major challenge for the study of morphogenesis now is to objectively define tissue sub-regions exhibiting different dynamics. Here we propose a method to automatically divide a tissue into regions where the local deformation rate is homogeneous. This was achieved by several steps including image segmentation, clustering, and region boundary smoothing. We illustrate the use of the pipeline using a large dataset obtained during the metamorphosis of the Drosophila pupal notum. We also adapt it to determine regions where the time evolution of the local deformation rate is homogeneous. Finally, we generalize its use to find homogeneous regions for the cellular processes such as cell division, cell rearrangement, or cell size and shape changes. We also illustrate it on wing blade morphogenesis. This pipeline will contribute substantially to the analysis of complex tissue shaping and the biochemical and bio-mechanical regulations driving tissue morphogenesis. 1 Summary statementTissue morphogenesis is driven by multiple mechanisms. This study proposes a methodology to identify regions in the developing tissue, where each of the regions has distinctive cellular dynamics and deformation.

developmental biology↗

bioRxiv2019

Lumen expansion facilitates epiblast-primitive endoderm fate specification in the mouse blastocyst formation.

Mouse blastocyst formation involves lumen formation and cell fate specification. While many studies have investigated how the blastocyst cell lineages are specified through genetics and signaling, studies into the potential role of the fluid lumen have yet to be conducted. We discover that blastocyst fluid emerges by secretion of cytoplasmic vesicles to intercellular space in addition to trans-epithelial flow. We observe that the beginning of epiblast and primitive endoderm spatial segregation directly follows lumen coalescence. Notably, we show that perturbing lumen expansion by pharmacological and biophysical means impair the specification and spatial segregation of primitive endoderm cells within the blastocyst. Combined, our results suggest that blastocyst lumen expansion plays a critical role in guiding cell fate specification and positioning. As epithelial tissues typically form lumina, lumen expansion may provide a general mechanism of cell fate control in many tissues.

developmental biology↗

bioRxiv2017

Collective cell migration without proliferation: density determines cell velocity and wave velocity

Collective cell migration contributes to morphogenesis, wound healing or tumor metastasis. Culturing epithelial monolayers on a substrate enables to quantify such tissue migration. By using narrow strips, we stabilise the front shape; by inhibiting cell division, we limit density increase and favor steady migration; by using long strips, we observe a confined cell monolayer migrating over days. A coherent collective movement propagates over millimeters; cells spread and density decreases from the monolayer bulk toward the front. Cell velocity ([~]micrometer per minute) increases linearly with cell radius, and does not depend explicitly on the distance to the front. Over ten periods of backwards propagating velocity waves, with wavelength [~]millimeter, are detected with a signal-to-noise ratio enabling for quantitative spatio-temporal analysis. Their velocity ([~]ten micrometers per minute) is ten times the cell velocity; it increases linearly with the cell radius. Their period ([~]two hours) is spatially homogeneous, and increases with the front density. When we inhibit the formation of lamellipodia, cell velocity drops while waves either disappear, or have a smaller amplitude and slower period. Our phenomenological model assumes that both cell and wave velocities are related with the activity of lamellipodia, and that the local stretching in the monolayer bulk modulates traction stresses. We find that parameter values close to the instability limit where waves appear yield qualitative and quantitative predictions compatible with experiments, including the facts that: waves propagate backwards; wave velocity increases with cell radius; lamellipodia inhibition attenuates, slows down or even suppresses the waves. Together, our experiments and modelling evidence the importance of lamellipodia in collective cell migration and waves.

biophysics↗