Biology subjects

Jelier, R.

Publications and source records attributed to Jelier, R..

10 recordsLinked to original sources

bioRxiv2026

Choreographed morphogenetic events underlie early foregut development in the mouse embryo

Between embryonic days 7.5 and 8.5, the mouse embryo undergoes a dramatic rearrangement of its entire anterior, a process known as ventral folding: the near-simultaneous morphogenesis of the cardiac crescent, cranial headfolds, and anterior foregut that together establish the antero-ventral body plan. While cardiac morphogenesis has been studied in detail, the cellular and mechanical basis of foregut involution remains largely undefined. Using combined light-sheet and spinning-disk live imaging spanning the full window of foregut formation, we show that involution proceeds through a stereotyped morphological programme that does not require actomyosin contractility for its initiation. Additionally, involution is preceded by a spatiotemporally restricted wave of apoptosis in embryonic visceral endoderm (emVE) cells, which extrude bidirectionally. A lineage- and stage-resolved bulk RNA-sequencing of emVE, definitive endoderm, and epiblast populations identifies a differential-adhesion and cell-cycle signature underlying this behaviour. Revisiting a visceral-endoderm-specific Bmp2 knock-out mutant, we find that BMP2 controls involution indirectly, by directing notochord positioning and thereby the geometry of the surrounding heart and headfold mechanics. Together, these findings reframe ventral folding as a single coordinated geometric process rather than a set of independent organ forming events.

developmental biology↗

bioRxiv2026

Evolution of an Aurora Kinase A Inhibitor from an Essential tRNA Synthetase

Gene duplication is a major driver of evolution, yet how it generates fundamentally new molecular functions remains poorly understood. Here, we show how such novelty arose in KLMT-1, a selfish toxin that causes genetic incompatibilities in Caenorhabditis tropicalis. KLMT-1 evolved via duplication of an essential tRNA synthetase but, strikingly, lost its ancestral role in tRNA biology and translation. Instead, KLMT-1 localizes to centrosomes, where it targets Aurora kinase A (AIR-1). This innovation is mediated by a three-amino acid insertion that extends a {beta}-hairpin loop, enabling electrostatic interaction with a regulatory interface on the kinase. Our results demonstrate how changes in selective pressure, combined with minimal modifications in neutrally evolving regions, allow duplicated proteins to access new functional space and evolve entirely new molecular activities.

evolutionary biology↗

bioRxiv2026

Integrated quantitative imaging and biomechanical modeling of early gastrulation in C. elegans

1The stereotyped internalization of two endodermal precursors during early Caenorhabditis elegans gastrulation enables quantitative dissection of cell ingression mechanics. Experimental work has shown that apical constriction drives Ea and Ep ingression, and several molecular features involved have been identified. Yet, no integrative mechanical analysis has assessed how these elements collectively produce the observed behavior. To address this, we combined biomechanical simulations with a comprehensive dataset of 3D-segmented cell meshes, some with cortical protein distributions, to analyze the mechanics of ingression in its in-vivo context. Our analysis shows the process starts shortly after birth of the ingressing cells. A cortical flow drives the formation of an E-cadherin-rich structure at the apical Ea-Ep interface, which contributes to localizing the buildup of apical tension. Simulations show that medioapical actomyosin contraction can reproduce the observed ingression movements and suggest force transmission to neighboring cells via a friction-based molecular clutch at the apical ring of contact. A series of concurrent cell divisions facilitates ingression, and their stereotyped planar orientation also contributes. Furthermore, we observe an embryo-wide movement of cells during gastrulation. This movement resembles a flow, suggesting that local force generation leads to global rearrangements via internal pressure changes. Finally, at the end of ingression, detailed microscopy shows that neighboring cells actively close the gastrulation cleft by forming a rosette-like configuration and extending actin-rich protrusions. In conclusion, our integrated mechanical description of gastrulation shows that successful ingression is driven by apical constriction and supported by localized friction-based force transmission, coordinated stereotyped cell divisions, and the resulting global tissue flow.

developmental biology↗

bioRxiv2026

Nematic structures contribute to robust zygotic polarization in C. elegans

The C. elegans zygote is a powerful model for asymmetric cell division. Its strikingly patterned cortex features thick F-actin bundles and myosin foci, contractile nematic structures that drive characteristic surface ruffles. Early in the cell cycle, symmetry breaks near the sperm-contributed centrosomes, typically at the presumptive posterior pole, and is marked by local downregulation of contractility. This initiates a cortical flow that polarizes the cell and enables PAR proteins to establish anterior and posterior domains. While biochemical mechanisms maintaining these domains are well understood, the mechanical role of cortical architecture in polarization remains unclear. We developed a three-dimensional (3D) mechanical model of C. elegans zygote polarization that represents the actin bundles and myosin foci of the cortex as a network of stiff contractile filaments. We measured cortical flow with high spatiotemporal resolution by tracking myosin foci, and used these data alongside mechanical properties from the literature to parametrize the model. The model simulates the complete polarization process in 3D, from symmetry breaking through domain stabilization, and reproduces key cortical dynamics including flow profiles, surface ruffles, and tension anisotropy. Domain arrest near the embryo midpoint emerges from density-dependent contractility regulation, in which cortical material redistribution during flow creates a mechanical negative feedback that balances anterior and posterior tension.We find that compressive flow aligns actin bundles in the anterior domain and generates anisotropic tension perpendicular to the flow direction. Although this alignment is not essential for polarization when symmetry breaking occurs at the pole, it contributes to this process when symmetry breaking occurs laterally. In such cases, anisotropic tension from aligned bundles drives axis convergence by rotating the posterior domain towards the nearest pole. Nematic cortical structures therefore ensure robust alignment of the polarization axis. AvailabilityAll data and code required to reproduce the results are freely available at https://doi.org/10.5281/zenodo.18135771. The latest version of the software is maintained at https://bitbucket.org/pgmsembryogenesis/polarization.

developmental biology↗

bioRxiv2023

Image-based force inference by biomechanical simulation

During morphogenesis, cells precisely generate forces that drive cell shape changes and cellular motion. These forces predominantly arise from contractility of the actomyosin cortex, allowing for cortical tension, protrusion formation, and cell division. Image-based force inference can derive such forces from microscopy images, without complicated and time-consuming experimental set-ups. However, current methods do not account for common effects, such as physical confinement and local force generation. Here we propose a force-inference method based on a biophysical model of cell shape, and assess relative cellular surface tension, adhesive tension between cells, as well as cytokinesis and protrusion formation. We applied our method on fluorescent microscopy images of the early C. elegans embryo. Predictions for cell surface tension at the 7-cell stage were validated by measurements using cortical laser ablation. Our non-invasive method facilitates the accurate tracking of force generation, and offers many new perspectives for studying morphogenesis. Author summaryAn important challenge in understanding morphogenesis is to determine where forces are generated. Force generation, such as differential cortical tension, plays a key role in cellular self-organization. However, measuring these forces experimentally is a big challenge that typically requires complicated experiments and direct access to the cells being investigated. A non-invasive method, such as force inference based on cell shapes, would have important advantages. Unfortunately, current methods can only be applied in certain cases. Here, we describe a more flexible 3D force inference method, FIDES, that can account for physical confinement, cell divisions and protrusions. We applied the method to infer forces throughout early C. elegans embryogenesis. By using cortical laser ablations, we confirmed that FIDES correctly inferred cell surface tensions in a dynamic stage of the nematodes embryogenesis. Our approach offers a route to routinely infer force generation in complex movements during morphogenesis, with microscopy images of cell shapes as the sole experimental input.

bioinformatics↗

bioRxiv2022

Cell shape characterization, alignment and comparison using FlowShape

MotivationThe shape of a cell reflects, among other things, actomyosin activity and adhesion properties. Cell shape is further tightly linked to cell differentiation and can reveal important cellular behaviors such as polarization. Hence, it is useful and informative to link cell shape to genetic and other perturbations. However, most currently used cell shape descriptors capture only simple geometric features such as volume and sphericity. We propose FlowShape, a new framework to study cell shapes in a complete and generic way. ResultsIn our framework a cell shape is first represented as a single function on a sphere. The curvature of the shape is measured and next mapped onto a sphere in a conformal manner. This special curvature map is then approximated by a series expansion: the spherical harmonics decomposition. This decomposition facilitates a wide range of shape analyses, including shape alignment, statistical cell shape comparison and inference of cell shape deformations over time. From this representation, we can reconstruct the cell shape using the Dirac equation. The new tool is applied to perform a complete, generic analysis of cell shapes, using the early Caenorhabditis elegans embryo as a model case. We distinguish and characterize the cells at the seven-cell stage. Next, a filter is designed to identify protrusions on the cell shape to highlight lamellipodia in cells. Furthermore, we use our framework to identify any shape changes following a gene knockdown of the Wnt pathway. Cells are first optimally aligned using the fast Fourier transform, followed by calculating an average shape. Shape differences between conditions are next quantified and compared to an empirical distribution. Finally, we put forward a highly performant implementation of the core algorithm, as well as routines to characterize, align and compare cell shapes, through the open-source software package FlowShape. AvailabilityThe data and code needed to recreate the results are freely available at https://doi.org/10.5281/zenodo.7391185. The most recent version of the software is maintained at https://bitbucket.org/pgmsembryogenesis/flowshape/. Author summaryWe present FlowShape, a framework for cell shape analysis, based on the concept of spherical harmonics decomposition. This decomposition allows for any function defined on a sphere to be rewritten as a weighted sum of basis functions. Contrary to previous work, we use a single function to describe a shape, the mean curvature, which implies that the decomposition weights can be used as a complete shape description. The expression of a shape in this manner allows for very efficient calculations, as we illustrate with the C. elegans embryo as a model. The decomposition permits efficient comparison and alignment of shapes. We demonstrate this by clustering the cells in the early embryo and illustrating the different shapes by cluster. The decomposition further facilitates averaging of shapes and searching for particular features on the shape by defining filters that can then be efficiently applied. Finally, we illustrate how the framework can facilitate statistical comparisons between shapes.

bioinformatics↗

bioRxiv2022

Stability of asymmetric cell division under confinement: A deformable cell model of cytokinesis applied to C. elegans development

Cell division during early embryogenesis has been linked to key morphogenic events such as embryo symmetry breaking and tissue patterning. It is thought that boundary conditions together with cell intrinsic cues act as a mechanical "mold", guiding cell division to ensure these events are more robust. We present a novel computational mechanical model of cytokinesis, the final phase of cell division, to investigate how cell division is affected by mechanical and geometrical boundary conditions. The model reproduces experimentally observed furrow dynamics and predicts the volume ratio of daughter cells in asymmetric cell divisions based on the position and orientation of the mitotic spindle. We show that the orientation of confinement relative to the division axis modulates the volume ratio in asymmetric cell division and quantified the mechanical contribution of cortex mechanics, relative to the mechanical properties of the furrow ring. We apply this model to early C. elegans development, which proceeds within the confines of an eggshell, and simulate the formation of the three body axes via sequential (a)symmetric divisions up until the six cell stage. We demonstrate that spindle position and orientation alone can be used to predict the volume ratio of daughter cells during the cleavage phase of development. However, for compression perturbed egg geometries, the model predicts that the change in confinement alone is insufficient to explain experimentally observed differences in cell volume, inferring an unmodeled underlying spindle positioning mechanism. Finally, the model predicts that confinement stabilizes asymmetric cell divisions against bubble-instabilities, which can arise due to elevated mitotic cortical tension. Author summaryA crucial morphogenic step during early embryonic development is symmetry breaking in the embryo. For C. elegans the formation of the three body axes can be traced back to the six cell stage, where tissue-topology is the result of symmetric and asymmetric divisions. How cell mechanical boundary conditions and cell intrinsic cues influence this process of symmetry breaking is still an open question, as currently, a quantitative mechanical description of cytokinesis in complex architectures is lacking. We developed a simple mechanical model of cell division, incorporated in an existing mechanical cortex model, to simulate cytokinesis in geometrically confined environments. Our approach was able to both capture furrow ring dynamics and predict the volume ratio of daughter cells accurately. By simulating early C. elegans development with different geometrical boundary conditions, we were able to trace back the origin of volume discrepancies between the experimental setups to a quantifiable shift in spindle positioning during cytokinesis. Finally, we showed how embryo confinement partially stabilizes bubble-instabilities that arise during asymmetric cell division during the early cleavage phase.

biophysics↗

bioRxiv2021

Physically asymmetric division of the C. elegans zygote ensures invariably successful embryogenesis

Asymmetric divisions that yield daughter cells of different sizes are frequent during early embryogenesis, but the importance of such a physical difference for successful development remains poorly understood. Here, we investigated this question using the first division of C. elegans embryos, which yields a large AB cell and a small P1 cell. We equalized AB and P1 sizes using acute genetic inactivation or optogenetic manipulation of the spindle positioning protein LIN-5. We uncovered that only some embryos tolerated equalization, and that there was a size asymmetry threshold for viability. Cell lineage analysis of equalized embryos revealed an array of defects, including faster cell cycle progression in P1 descendants, as well as defects in cell positioning, division orientation and cell fate. Moreover, equalized embryos were more susceptible to external compression. Overall, we conclude that unequal first cleavage is essential for invariably successful embryonic development of C. elegans.

cell biology↗

bioRxiv2019

Neuromedin U signaling regulates memory retrieval of learned salt avoidance in a C. elegans gustatory circuit

Learning and memory are regulated by neuromodulatory pathways, but the contribution and temporal requirement of most neuromodulators in a learning circuit are unknown. Here we identify the evolutionarily conserved neuromedin U (NMU) neuropeptide family as a regulator of memory retrieval in C. elegans gustatory aversive learning. The NMU homolog CAPA-1 and its receptor NMUR-1 are required for the expression of learned salt avoidance. Aversive learning depends on the release of CAPA-1 neuropeptides from sensory ASG neurons that respond to salt stimuli in an experience-dependent manner. Optogenetic silencing of CAPA-1 neurons blocks the immediate retrieval, but not the acquisition, of learned salt avoidance. CAPA-1 subsequently signals through NMUR-1 in AFD sensory neurons to modulate two navigational strategies for salt chemotaxis. Aversive conditioning thus recruits NMU signaling to eventually modulate locomotor programs for expressing learned avoidance behavior. Because NMU signaling is conserved across bilaterian animals, our findings incite further research into its function in other memory and decision-making circuits.\n\nGraphical Abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=195 SRC=\"FIGDIR/small/683888v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (58K):\norg.highwire.dtl.DTLVardef@10bf862org.highwire.dtl.DTLVardef@dfeb7eorg.highwire.dtl.DTLVardef@dda0b8org.highwire.dtl.DTLVardef@62bc95_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2018

Mitochondrial ubiquinone-mediated longevity is marked by reduced cytoplasmic protein translation

Mutations in the clk-1 gene impair mitochondrial ubiquinone biosynthesis and extend the lifespan of C. elegans. We demonstrate here that this life extension is linked to the repression of cytoplasmic protein translation. Clk-1 mutations inhibit polyribosome formation similarly to daf-2 mutations that dampen insulin signaling. Comparisons of total versus polysomal RNAs in clk-1 mutants reveal a reduction in the translational efficiencies of mRNAs coding for elements of the translation machinery and an increase in those coding for the oxidative phosphorylation and autophagy pathways. Knocking down the transcription initiation factor TAF-4, a protein that becomes sequestered in the cytoplasm during early embryogenesis to induce transcriptional silencing, ameliorates the clk-1 inhibition of polyribosome formation. These results underscore a prominent role for the repression of cytoplasmic protein translation in eukaryotic lifespan extension, and suggest that mutations impairing mitochondrial function are able to exploit this repression similarly to reductions of insulin signaling. Moreover, this report reveals an unexpected role for TAF-4 as a repressor of polyribosome formation when ubiquinone biosynthesis is compromised.

systems biology↗