Biology subjects

Iber, D.

Publications and source records attributed to Iber, D..

At least 19 recordsLinked to original sources

bioRxiv2026

OptiCell3D: Precise inference of mechanical cell properties from microscopy imaging

We introduce OptiCell3D, an open-source image-based framework for inferring cellular mechanical properties directly from 3D microscopy data. By integrating short physical simulations with gradient-based optimization via backpropagation, our method substantially improves accuracy compared to existing approaches. Moreover, OptiCell3D enables mechanical inference in tissues that are too large to be fully imaged, extending its applicability to more complex biological systems. We demonstrate the power of our approach by applying OptiCell3D to five morphologically diverse mouse epithelial tissues. By combining inferred parameters with simulations and morphometric analysis, we find that the ratio of apical to lateral surface tension predicts cell aspect ratio across epithelial subtypes, linking a single mechanical parameter to the broad morphological diversity of epithelia. Finally, we apply our framework to stratified tissues, finding greater variability in pressure and surface tension between cells and tension gradients along the apico-basal axis.

biophysics↗

bioRxiv2026

Determinants of the Transition Zone Width of Morphogen Readouts

In tissue patterning, cell fate boundaries often form transition zones with mixed or gradual fates rather than sharp demarcations. Traditionally, such zones in morphogen-driven systems were attributed to fluctuations in morphogen concentrations, especially at low molecule numbers. Here, we present experimental data from the mouse neural tube, the precursor of the central nervous system, which challenges this view. Contrary to expectations, we find that the transition zone width (TZW) does not increase with distance from the morphogen source. By combining experiments, theory, and computational modelling, we identify key factors shaping the TZW. Our findings suggest that cellular readout noise, rather than morphogen fluctuations, determine the TZW. The inferred variability in the parameters defining morphogen dynamics and cellular readout remains within previously reported physiological ranges. This discovery adds to earlier findings that morphogen gradients maintain higher-than-expected patterning precision over long distances, offering new insights into the robustness of developmental processes.

developmental biology↗

bioRxiv2025

Directed cell migration is a versatile mechanism for rapid developmental pattern formation

The evolution of multicellular organisms hinges on self-organization mechanisms that generate tissues with diverse functions. A central process is the breaking of symmetry to form spatial patterns from initially uniform conditions. Among the various mechanisms proposed, directed cell migration--driven by chemotaxis, durotaxis, differential adhesion or other processes--offers a compelling strategy to organize tissues rapidly and robustly. Here, we unify these concepts into a general mathematical framework and show that it can produce diverse spatial patterns across one-, two-, and three-dimensional domains. Using numerical simulations and stability theory, we characterize the emergence, geometry, and formation speed of these patterns. Our findings provide a mechanistic understanding of morphogenesis beyond the traditional chemical or mechanical patterning paradigms and offer a quantitative foundation to guide pattern formation in tissue engineering and regenerative medicine.

developmental biology↗

bioRxiv2025

The emergence of the fractal bronchial tree

The fractal design of the bronchial tree, as described by the Hess-Murray law, facilitates energy-efficient lung ventilation, yet its developmental origins remain unclear. Here, we quantify the rearrangement of the embryonic bronchial tree into its fractal architecture, using SkelePlex, a new neural network-based image processing pipeline, and elucidate the biophysical principles governing its formation. We find that the branch shapes are such that pressure drop, shear, axial and hoop stress are equal across all branches. The seemingly random diameter of sister branches reflects the different number of tips they connect to in the asymmetric lung tree. By analysing lungs after pneumonectomy and those affected by chronic obstructive pulmonary disease (COPD), we show the same principles to persist in adulthood and disease, potentially providing quantitative biomarkers for disease progression and therapeutic guidance.

developmental biology↗

bioRxiv2023

Morphogen gradients can convey position and time in growing tissues

During embryonic development, cells coordinate fate decisions based on both position and time. While morphogen gradients have long been recognized as a source of positional information, how timing is synchronized across developing tissues remains unclear. We propose a simple mechanism by which morphogen dynamics can also encode time. If the morphogen source expands with a uniformly growing tissue and the gradient maintains a constant decay length, cells experience transient, hump-shaped signals that convey timing cues. Moreover, when two opposing exponential gradients with equal lengths--such as those in the vertebrate neural tube--interact, their product forms a uniform signal that can synchronize fate decisions across the entire tissue. With increasing gradient amplitudes, cells encounter a transient signal; with constant amplitudes, the signal decays--a feature of a depletion timer. This mechanism provides a generalizable principle by which morphogen gradients may coordinate both spatial and temporal aspects of patterning during development.

developmental biology↗

bioRxiv2023

Morphometry and mechanical instability at the onset of epithelial bladder cancer

Malignancies of epithelial tissues, called carcinomas, account for the majority of cancer cases. Much cancer research has focused on genetic alterations and their relation to different carcinoma phenotypes. Besides a rewiring in the signalling networks, carcinoma progression is accompanied by mechanical changes in the epithelial cells and the extracellular matrix. Here, we reveal intricate morphologies in the basement membrane at the onset of bladder cancer, and propose that they emerge from a mechanical buckling instability upon epithelial overgrowth. Using a combination of microscopy imaging of the mouse and human bladder tissue, elasticity theory, and numerical simulations of differential growth in the bladder mucosa, we find that aberrant tissue morphologies can emerge through stiffness changes in the different mucosa layers. The resulting thickening, wrinkles and folds exhibit qualitative and quantitative similarity with imaged early papillary tumors and carcinomas in situ. Atomic force microscopy indeed reveals local stiffness changes in the pathological basement membrane. Our findings suggest a mechanical origin of the different carcinoma subtypes in the bladder, which have vastly different clinical prognosis. They might provide the basis for a new line of attack in medical carcinoma treatment and prophylaxis.

cancer biology↗

bioRxiv2023

3D Simulation of Tissue Mechanics with Cell Polarization

The 3D organisation of cells determines tissue function and integrity, and changes dramatically in development and disease. Cell-based simulations have long been used to define the underlying mechanical principles. However, large computational costs have so far limited simulations to either simplified cell geometries or small tissue patches. Here, we present SimuCell3D, a highly efficient open-source program to simulate large tissues in 3D with subcellular resolution, growth, proliferation, extracellular matrix, fluid cavities, nuclei, and non-uniform mechanical properties, as found in polarised epithelia. Spheroids, vesicles, sheets, tubes, and other tissue geometries can readily be imported from microscopy images and simulated to infer biomechanical parameters. Doing so, we show that 3D cell shapes in layered and pseudostratified epithelia are largely governed by a competition between surface tension and intercellular adhesion. SimuCell3D enables the large-scale in silico study of 3D tissue organization in development and disease at an unprecedented level of detail.

bioinformatics↗

bioRxiv2023

2D Effects Enhance Precision of Gradient-Based Tissue Patterning

Robust embryonic development requires pattern formation with high spatial accuracy. In epithelial tissues that are patterned by morphogen gradients, the emerging patterns achieve levels of precision that have recently been explained by a simple one-dimensional reaction-diffusion model with kinetic noise. Here, we show that patterning precision is even greater if transverse diffusion effects are at play in such tissues. The positional error, a measure for spatial patterning accuracy, decreases in wider tissues but then saturates beyond a width of about ten cells. This demonstrates that the precision of gradient-based patterning in two- or higher-dimensional systems can be even greater than predicted by 1D models, and further attests to the potential of noisy morphogen gradients for high-precision tissue patterning.

developmental biology↗

bioRxiv2022

The protooncogene Ski regulates the neuron-glia switch during development of the mammalian cerebral cortex

The brain is the most complex organ in mammals and understanding the origin of this complexity is a major challenge for developmental biologists. Crucial to the size and morphology of the cortex is the timing and transition of neural stem cell (NSC) fate. An interesting candidate for modulating and fine tuning these processes is the transcriptional regulator Ski, a protooncogene expressed in cortical cells. Ski is involved in diverse cellular processes and epigenetic programs, and mice deficient in Ski exhibit complex central nervous system defects that resemble some of the features observed in patients with 1p36 deletion syndrome and Shprintzen-Goldberg syndrome. Here, we took advantage of in vivo transgenic labeling and next-generation sequencing to analyze the gene expression profiles of NSCs, basal progenitor (BP) cells, and newborn neurons (NBNs) from wildtype and Ski-deficient embryos throughout cortical development. We created a unique database that allowed us to identify and compare signaling pathways and transcriptional networks within each progenitor population in the presence and absence of Ski. We find that NSCs are the most affected cell population and uncover that mutant NSCs fail to switch to a gliogenic fate in time. We show that Ski functions in concert with the Bone Morphogenetic Protein (BMP) signaling pathway to alter the cell differentiation fate of NSCs from neurons to glia, which is key to generating adequate numbers of specific cell types during corticogenesis. Thus, by combining genetic tools and bioinformatic analysis, our work not only deepens the knowledge of how Ski functions in the brain, but also provides an immense resource for studying neurodevelopmental disorders.

systems biology↗

bioRxiv2022

Patterning precision under non-linear morphogen decay and molecular noise

Morphogen gradients can instruct cells about their position in a patterned tissue. Non-linear morphogen decay has been suggested to increase gradient precision by reducing the sensitivity to variability in the morphogen source. Here, we use cell-based simulations to quantitatively compare the positional error of gradients for linear and non-linear morphogen decay. While we confirm that non-linear decay reduces the positional error close to the source, the reduction is very small for physiological noise levels. Far from the source, the positional error is much larger for non-linear decay in tissues that pose a flux barrier to the morphogen at the boundary. In light of this new data, a physiological role of morphogen decay dynamics in patterning precision appears unlikely.

developmental biology↗

bioRxiv2022

Geometric Effects Position Renal Vesicles During Kidney Development

During kidney development, reciprocal signalling between the epithelium and the mesenchyme coordinates nephrogenesis with branching morphogenesis of the collecting ducts. The mechanism that positions the renal vesicles, and thus the nephrons, relative to the branching ureteric buds has remained elusive. By combining computational modelling and experiments, we show that geometric effects concentrate the key regulator, WNT9b, at the junctions between parent and daughter branches where renal vesicles emerge, even when uniformly expressed in the ureteric epithelium. This curvature effect might be a general paradigm to create non-uniform signalling in development.

developmental biology↗

bioRxiv2022

Identification and implication of tissue-enriched ligands in epithelial-endothelial crosstalk during pancreas development

Development of the pancreas is driven by an intrinsic program coordinated with signals from other cell types in the epithelial environment. These intercellular communications have been so far challenging to study because of the low concentration, localized production and diversity of the signals released. Here, we combined scRNAseq data with a computational interactomic approach to identify signals involved in the reciprocal interactions between the various cell types of the developing pancreas. This in silico approach yielded 40,607 potential ligand-target interactions between the different main pancreatic cell types. Among this vast network of interactions, we focused on three ligands potentially involved in communications between epithelial and endothelial cells. Bmp7 and Wnt7b, expressed by pancreatic epithelial cells and predicted to target endothelial cells, and Sema6d, involved in the reverse interaction. In situ hybridization confirmed the localized expression of Bmp7 in the pancreatic epithelial tip cells and of Wnt7b in the trunk cells. On the contrary, Sema6d was enriched in endothelial cells. Functional experiments on ex vivo cultured pancreatic explants indicated that tip cell-produced Bmp7 restrained development of endothelial cells. This work identified ligands with a restricted tissular and cellular distribution and highlighted the role of Bmp7 in the intercellular communications shaping vessel development during pancreas organogenesis.

developmental biology↗

bioRxiv2022

FollicleFinder: automated three-dimensional segmentation of human ovarian follicles

In vitro fertilization (IVF) treatment protocols require frequent monitoring of the ovarian follicle growth process. We report FollicleFinder, an open source pipeline for the automated, 3D segmentation of ovarian follicles. FollicleFinder also accurately measures clinically-relevant morphological properties such as diameter, surface area, and volume. AvailabilityThe FollicleFinder pipeline is available at https://git.bsse.ethz.ch/iber/ovary-analysis and the graphical user interface is available at https://git.bsse.ethz.ch/iber/follicle-tracker.

bioinformatics↗

bioRxiv2022

Temporal and sequential transcriptional dynamics define lineage shifts in corticogenesis

The cerebral cortex contains billions of neurons, and their disorganization or misspecification leads to neurodevelopmental disorders. Understanding how the plethora of projection neuron subtypes are generated by cortical neural stem cells (NSCs) is a major challenge. Here, we focused on elucidating the transcriptional landscape of murine embryonic NSCs, basal progenitors (BPs) and newborn neurons (NBNs) throughout cortical development. We uncover dynamic shifts in transcriptional space over time, and heterogeneity within each progenitor population. We identified signature hallmarks of NSC, BP and NBN clusters, and predict active transcriptional nodes and networks that contribute to neural fate specification. We find that the expression of receptors, ligands and downstream pathway components is highly dynamic over time and throughout the lineage implying differential responsiveness to signals. Thus, we provide an expansive compendium of gene expression during cortical development that will be an invaluable resource for studying neural developmental processes and neurodevelopmental disorders.

neuroscience↗

bioRxiv2022

FGF8 induces chemokinesis and regulates condensation of mouse nephron progenitor cells

Kidneys develop via iterative branching of the ureteric epithelial tree and subsequent nephrogenesis at the branch points. Nephrons form in the cap mesenchyme as the metanephric mesenchyme (MM) condenses around the epithelial ureteric buds (UBs). Previous work demonstrated that FGF8 is important for the survival of nephron progenitor cells (NPCs), and early deletion of Fgf8 leads to the cessation of nephron formation, which results in post-natal lethality. We now reveal a novel function of FGF8. By combining transgenic mouse models, quantitative imaging assays, and data-driven computational modelling, we show that FGF8 has a strong chemokinetic effect and that this chemokinetic effect is important for the condensation of NPCs to the UB. The computational model shows that the motility must be lower close to the UB to achieve NPC attachment. We conclude that the FGF8 signalling pathway is crucial for the coordination of NPCs behaviour to the UB. Chemokinetic effects have been described also for other FGFs and may be relevant more generally for the formation of mesenchymal condensations.

developmental biology↗

bioRxiv2022

Impact of cell size on morphogen gradient precision

Tissue patterning during embryonic development is remarkably precise. We numerically determine the impact of the cell diameter, gradient length, and the morphogen source on the variability of morphogen gradients and show that the positional error increases with the gradient length relative to the size of the morphogen source, and with the square root of the cell diameter and the readout position. We provide theoretical explanations for these relationships, and show that they enable high patterning precision over developmental time for readouts that scale with expanding tissue domains, as observed in the Drosophila wing disc. Our analysis suggests that epithelial tissues generally achieve higher patterning precision with small cross-sectional cell areas. An extensive survey of measured apical cell areas shows that they are indeed small in developing tissues that are patterned by morphogen gradients. Enhanced precision may thus have led to the emergence of pseudostratification in epithelia, a phenomenon for which the evolutionary benefit had so far remained elusive.

developmental biology↗

bioRxiv2021

Hingepoint emergence in mammalian spinal neurulation

Neurulation is the process in early vertebrate embryonic development during which the neural plate folds to form the neural tube. Spinal neural tube folding in the posterior neuropore changes over time, first showing a median hingepoint, then both the median hingepoint and dorsolateral hingepoints, followed by dorsolateral hingepoints only. The biomechanical mechanism of hingepoint formation in the mammalian neural tube is poorly understood. Here, we employ a mechanical finite element model to study neural tube formation. The computational model mimics the mammalian neural tube using microscopy data from mouse and human embryos. While intrinsic curvature at the neural plate midline has been hypothesized to drive neural tube folding, intrinsic curvature was not sufficient for tube closure in our simulations. We achieved neural tube closure with an alternative model combining mesoderm expansion, non-neural ectoderm expansion and neural plate adhesion to the notochord. Dorsolateral hingepoints emerged in simulations with low mesoderm expansion and zippering. We propose that zippering provides the biomechanical force for dorsolateral hingepoint formation in settings where the neural plate lateral sides extend above the mesoderm. Together, these results provide a new perspective on the biomechanical and molecular mechanism of mammalian spinal neurulation.

developmental biology↗

bioRxiv2021

Development of a 3D atlas of the embryonic pancreas for topological and quantitative analysis of heterologous cell interactions

Generating comprehensive image maps, while preserving spatial 3D context, is essential to quantitatively assess and locate specific cellular features and cell-cell interactions during organ development. Despite the recent advances in 3D imaging approaches, our current knowledge of the spatial organization of distinct cell types in the embryonic pancreatic tissue is still largely based on 2D histological sections. Here, we present a light-sheet fluorescence microscopy approach to image the pancreas in 3D and map tissue interactions at key development time points in the mouse embryo. We used transgenic mouse models and antibodies to visualize the three main cellular components within the developing pancreas, including epithelial, mesenchymal and endothelial cell populations. We demonstrated the utility of the approach by providing volumetric data, 3D distribution of distinct progenitor populations and quantification of relative cellular abundance within the tissue. Lastly, our image data were combined in an open source online repository (referred to as Pancreas Embryonic Cell Atlas). This image dataset will serve the scientific community by enabling further investigation on pancreas organogenesis but also for devising strategies for the in vitro generation of transplantable pancreatic tissue for regenerative therapies.

developmental biology↗