Biology subjects

van Bavel, C.

Publications and source records attributed to van Bavel, C..

4 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↗

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↗