Biology subjects

Erzberger, A.

Publications and source records attributed to Erzberger, A..

10 recordsLinked to original sources

bioRxiv2026

The limits of scaling in aggregation-driven patterning of cell collectives

Robust development requires maintaining correct proportions as overall size varies. What controls and limits this scaling remains poorly understood due to the complex interplay of mechanical and biochemical embryonic factors. Combining confinement of dissociated embryonic presomitic mesoderm cells with imaging and chemical perturbations, we identified cell aggregation as the initial event in de novo posterior pole formation. Using a continuum model based solely on cell-cell attraction, we quantitatively map how the time available for aggregation-driven patterning limits the maximum scalable system size. Small systems allow rapid, robust pattern scaling, whereas coarsening dynamics substantially delay scaled patterns in large systems. Our experiments quantitatively confirm these predicted scaling regimes. Together, our results reveal a developmental time-size tradeoff governing the scaling of aggregation-driven patterns.

biophysics↗

bioRxiv2025

Boundary-guided cell alignment drives mouse epiblast maturation

Symmetry breaking and pattern formation are critical events that occur throughout embryonic development. In early mouse development, a mass of non-polarized epiblast (EPI) cells in the blastocyst forms the egg-cylinder, while cells become apico-basally polarized and build a radial configuration. Yet, what drives the formation of this tissue architecture remains unclear. Here, we demonstrate that orientational patterning of EPI cells is dictated by heterogeneous tissue boundaries, which then defines central lumen positioning. We show that EPI cells progressively orient perpendicular to the visceral endoderm (VE) boundary enriched with laminin and active integrin {beta}1, but parallel to the extraembryonic ectoderm interface. These orientation dynamics are consistent with general boundary-induced alignment effects in polar materials, with a topological defect predicting the position where the pro-amniotic cavity nucleates. Knockout of laminin {gamma}1 and integrin {beta}1 confirms the essential role of adhesion at the EPI-VE-boundary. The established EPI pattern, in turn, facilitates ERK activation to ensure proper EPI maturation. Together, these findings present the mechanistic basis and functional significance of EPI tissue patterning.

developmental biology↗

bioRxiv2024

Nuclear deformability facilitates apical nuclear migration in the developing zebrafish retina

Nuclear positioning is an important aspect of cell and developmental biology. One example is the apical positioning of nuclei in retinal and other neuroepithelia. Here, apical nuclear migration is crucial for correct tissue formation. Cytoskeletal mechanisms that drive nuclei to the apical side have been explored. Yet, whether also nuclear properties influence apical nuclear migration remained comparatively less understood. Lamin A/C expression levels have been shown to be directly related to nuclear deformability. Further, it was shown that many nuclei in early development, including neuroepithelial nuclei, express only low levels of Lamin A/C. Thus, we asked whether increased expression of Lamin A in the densely packed zebrafish retinal neuroepithelium affects nuclear migration phenomena. We find that overexpressing Lamin A in retinal nuclei of single cells or in the whole tissue increased nuclear stiffness and consequently impaired apical positioning. Interestingly, also nuclei of control cells embedded in a Lamin A overexpressing environment displayed impaired apical nuclear migration. When Lamin A is overexpressed at the tissue level this further leads to a delay in mitotic entry. Thus, nuclear material properties, within cells but also in the surrounding environment, can influence nuclear and cell behavior in densely packed neuroepithelia. Overall, this work quantitatively shows a relevance of low Lamin A/C levels in early neuroepithelial development. These findings are most likely also applicable for other developing tissues which feature nuclear and cell motion through crowded environments.

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

COORDINATION BETWEEN EMBRYO GROWTH AND TROPHOBLAST MIGRATION UPON IMPLANTATION DELINEATES MOUSE EMBRYOGENESIS

Implantation marks a key transition in mammalian development. The role of embryo-uterus interaction in periimplantation development is however poorly understood due to inaccessibility in utero. Here, we develop an engineered uterus-like microenvironment to recapitulate mouse development ex vivo up to E5.25 and discover an essential role of integrin-mediated trophoblast adhesion to the uterine matrix. Light-sheet microscopy shows that trophoblast cells undergo Rac1-dependent collective migration upon implantation, displacing Reicherts membrane and generating space for egg cylinder growth. The key role of coordination between trophoblast migration and embryo growth is verified by experimentally manipulating the migration velocity and geometry of the engineered uterus. Modeling the implanting embryo as a wetting droplet links the tissue shape dynamics to underlying changes in trophoblast adhesion and suggests that the corresponding tension release facilitates egg cylinder formation. Together, this study provides mechanisms by which dynamic embryo-uterus interactions play an essential role in peri-implantation development.

developmental biology↗

bioRxiv2021

A robust ex vivo system to study cellular dynamics underlying mouse peri-implantation development

Upon implantation, mammalian embryos undergo major morphogenesis and key developmental processes such as body axis specification and gastrulation. However, limited accessibility obscures study of these crucial processes. Here, we develop an ex vivo Matrigel-collagen-based culture to recapitulate mouse development from E4.5 to 6.0. Our system not only recapitulates embryonic growth, axis initiation, and overall 3D architecture in 49% of cases, its compatibility with light-sheet microscopy enables study of cellular dynamics through automatic cell segmentation. We find that upon implantation, release of the increasing tension in the polar trophectoderm is necessary for its constriction and invagination. The resulting extra-embryonic ectoderm plays a key role in growth, morphogenesis and patterning of the neighboring epiblast, which subsequently gives rise to all embryonic tissues. This 3D-ex vivo system thus offers an unprecedented access to peri-implantation development for in toto monitoring, measurement and spatio-temporally controlled perturbation, revealing a mechano-chemical interplay between extra-embryonic and embryonic tissues.

developmental biology↗

bioRxiv2021

Curvature sensing steers actin-driven cell migration

Cell migration is a hallmark out-of-equilibrium process in biology. In addition to persistent self-propelled motion, many cells display remarkable adaptive behaviors when they navigate complex environments within the body. Combining theory and experiments, we identify a curvature-sensing mechanism underlying obstacle avoidance in immune-like cells. The genetic perturbation of this machinery leads to a reduced capacity to evade obstructions combined with faster and more persistent cell migration in obstacle-free environments. We propose that the active polymerization of the actin cytoskeleton at the advancing edge of migrating cells is locally inhibited by the curvature-sensitive BAR protein Snx33 in regions with inward plasma membrane curvature. This coupling between actin and membrane dynamics leads to a mechanochemical instability that generates complex protrusive patterns at the cellular front. Adaptive motility thus arises from two simultaneous curvature-dependent effects, i) the specific reduction of propulsion in regions where external objects deform the plasma membrane and ii) the intrinsic patterning capacity due to the membrane-actin coupling that promotes spontaneous changes in the cells protrusions. Our results show how cells utilize actin- and plasma membrane biophysics to sense their environment, allowing them to adaptively decide if they should move ahead or turn away. On the basis of our findings, we propose that the natural diversity of BAR proteins may allow cells to tune their curvature sensing machinery to match the shape characteristics in their environment.

cell biology↗

bioRxiv2019

Symmetry breaking during morphogenesis of a mechanosensory organ

Actively regulated symmetry breaking, which is ubiquitous in biological cells, underlies phenomena such as directed cellular movement and morphological polarization. Here we investigate how an organ-level polarity pattern emerges through symmetry breaking at the cellular level during the formation of a mechanosensory organ. Combining theory, genetic perturbations, and in vivo imaging assisted by deep learning, we study the development and regeneration of the fluid-motion sensors in the zebrafishs lateral line. We find that two interacting symmetry-breaking events -- one mediated by biochemical signaling and the other by cellular mechanics -- give rise to a novel form of collective cell migration, which produces a mirror-symmetric polarity pattern in the receptor organ.

biophysics↗

bioRxiv2019

Tissue shape determines actin-dependent nuclear migration mechanisms in neuroepithelia

Correct nuclear position is crucial for cellular function. Depending on cell context however, cytoskeletal elements and force generation mechanisms vary. While these mechanisms have been intensely studied in single cells, how nuclear positioning is linked to tissue morphology is less clear. Here, we compare apical nuclear positioning in developing straight and curved neuroepithelia of zebrafish. Interestingly, in differently shaped neuroepithelia the kinetics of nuclear positioning differ and we find that distinct actin-dependent mechanisms are employed. In straight neuroepithelia nuclear positioning is controlled by Rho-ROCK-dependent myosin contractility. Curved neuroepithelia use a formin-dependent pushing mechanism for which we propose a force generation theory. We suggest that cytoskeleton adaptability to tissue shape ensures correct nuclear positioning and robust epithelial maturation across different geometries. We further speculate that different mechanisms arise due to differences in actin arrangements during development, a theme highlighting the importance of developmental context for the execution of intracellular processes.

cell biology↗

bioRxiv2018

Notch-Mediated Polarity Decisions in Mechanosensory Hair Cells

The development of mechanosensory epithelia, such as those of the auditory and vestibular systems, results in the precise orientation of mechanosensory hair cells and consequently directional sensitivity. After division of a precursor cell in the zebrafishs lateral line, the daughter hair cells differentiate with opposite mechanical sensitivity. Through a combination of theoretical and experimental approaches, we show that Notch1a-mediated lateral inhibition produces a bistable switch that reliably gives rise to cell pairs of opposite polarity. Using our mathematical model of the process, we predict the outcome of several genetic and chemical alterations to the system, which we then confirm experimentally. We show that Notch1a downregulates the expression of Emx2, a transcription factor known to be involved in polarity specification, and acts in parallel with the planar-cell-polarity system to determine the orientation of hair bundles. By analyzing the effect of simultaneous genetic perturbations to Notch1a and Emx2 we infer that the generegulatory network determining cell polarity includes undiscovered polarity effectors.

developmental biology↗