Biology subjects

Braun, E.

Publications and source records attributed to Braun, E..

At least 19 recordsLinked to original sources

bioRxiv2026

Hidden Dynamical Canalization at the Onset of Hydra Morphogenesis

The primary morphological transition in Hydra regeneration, from a quasi-spherical fragment to an elongated body, is preceded by a prolonged period during which its average form changes only modestly, while its instantaneous shape continues to fluctuate. We asked whether this preparatory stage contains signatures of dynamical organization. Using principal component analysis, we calculated the effective dimension of shape fluctuations, which characterizes how broadly they are distributed across PCA directions. Across all five conditions, spanning differences in tissue fragment size, axial origin and GdCl exposure, the effective dimension decreased progressively before overt tissue elongation. Total fluctuation variance increased about 2.8-fold, whereas the leading eigenvalue increased about fourfold. Late intervals had lower effective dimension than early intervals at similar coarse shapes. Calcium analysis in GdCl-treated tissues distinguished mean level, fast events and spatial heterogeneity. Fast events were associated with short-timescale shape changes. After accounting for temporal trends, mean Ca2+ and coarse morphology, higher spatial heterogeneity of Ca2+ activity was associated with lower effective dimension. The progressive concentration of morphological fluctuations along fewer dominant directions characterizes dynamical canalization associated with spatial Ca2+ heterogeneity.

biophysics↗

bioRxiv2026

Phlag: Scalable detection of genomics regions with unexplained phylogenetic heterogeneity

MotivationPhylogenetic analyses of entire genomes (phylogenomics) have revealed abundant heterogeneity of evolutionary histories. While much has been done to model this heterogeneity and to infer species trees despite it, the current toolkit has a limitation. Most methods assume that gene trees across the genome differ but are all sampled from the same distribution, defined by models such as the multi-species coalescent (MSC), and parametrized consistently across the genome. Empirical data strongly suggest this assumption is often violated because the species tree, its parameters, or the process generating the gene trees can all change across the genome. Errors in the data can further compound this heterogeneity. ResultsTo address this challenge, we define the problem of detecting what segments of the genome are inconsistent with a putative species tree, even after allowing discordance according to MSC. We model gene trees not as a set, but rather as a series (a realization of a stochastic process) along genomic positions. We propose a Hidden Markov Model (HMM) approach applied to quartet statistics measured from gene trees and tie the model to MSC using simulations. The combined use of these three ideas leads to a scalable method called Phlag. On simulated and real data, we show that Phlag can detect many cases of change in underlying evolutionary processes, including reduced recombination rates, population size changes, and admixture, all using the same algorithm. Availability and ImplementationPhlag is available at github.com/bo1929/phlag. All results and scripts can be found at github.com/bo1929/shared.phlag.

evolutionary biology↗

bioRxiv2026

Rupture-Repair Cycles in Regenerating Hydra Tissues

Destructive mechanical breakdowns and fractures are ubiquitous events in driven physical matter; living tissues, by contrast, can rupture repeatedly while restoring integrity. Here we study rupture-repair interplay in regenerating Hydra tissues, which cycle through osmotic inflation, pressure release by rupture, and resealing. We utilize bright-field imaging of the tissues projected area as a readout of the rupture magnitude before it is arrested. Analyzing these event statistics, we find that the tail of the area-drop distribution is controlled by Ca2+-dependent repair efficiency. When the Ca2+ response is weakened, either by partially blocking gap-junctions mediating the intercellular communication, or by inhibiting stretch-activated Ca2+ channels, the actomyosin force that arrests the rupture process is delayed or reduced. Under these conditions, rare large pressure releases become more likely, and the tail of the distribution crosses over from an exponential behavior, exhibiting a characteristic scale, to a power-law one consistent with a critical-like regime reflecting intermittent rupture propagation. These results identify mechanically evoked Ca2+ activity as a control axis linking repair to rupture statistics in a living tissue. It supports a picture of rupture front advancing by stick-slip-like dynamics as it encounters a heterogeneous mechanical landscape, akin to failure-front propagation in disordered materials.

biophysics↗

bioRxiv2025

Origin, domestication, and diversity of the climate resilient Ethiopian cereal teff

Teff (Eragrostis tef) is a climate-resilient cereal and staple crop in the Horn of Africa, cultivated by millions of smallholder farmers. Despite its cultural and nutritional significance, teff has limited genomic tools, constraining progress in yield improvement and trait optimization. Here, we assembled and resequenced the Teff Association Panel (TAP), a diverse set of 265 landraces and cultivars, to investigate the domestication history, genetic diversity, and agronomic traits of teff. Phylogenetic and population genetic analyses confirm Eragrostis pilosa as the direct progenitor of teff, with domestication likely occurring in the Tigray region of Ethiopia. We generated a high-quality reference genome for E. pilosa and found extensive chromosomal collinearity and minimal gene loss compared to teff, with teff-specific genes enriched in functions related to domestication traits. We identified signatures of selection across the teff genome and used genome-wide association studies (GWAS) to map loci associated with seed color and panicle architecture. Integrated GWAS, expression, metabolic, and comparative genomic analyses pinpoint a major seed color locus containing orthologs of the TT7 cytochrome P450 gene involved in flavonoid hydroxylation and the TT2 MYB transcription factor regulating proanthocyanidin biosynthesis. For panicle architecture, we identified a strong association near a teff ortholog of Dense and Erect Panicle 1 (DEP1), a key regulator of inflorescence structure in rice and sorghum. This suggests convergent selection on shared genetic pathways controlling panicle morphology across cereals. Our findings confirm the evolutionary origin of teff, identify key domestication loci, and highlight untapped genetic diversity among Ethiopian breeding lines. These genomic resources provide a foundation for accelerating teff improvement through molecular breeding and genome editing to enhance yield, resilience, and nutrition.

plant biology↗

bioRxiv2025

Community resilience in a river network: the roles of connectivity and drying regime

The cross-scale resilience model suggests that resilience, the amount of disturbance an ecosystem can absorb before collapsing and reorganizing, can be measured by evaluating the diversity and redundancy of functions performed by species at different spatiotemporal scales. Yet, little is known about the effects of flow intermittence and associated hydrological connectivity on the resilience capacity of instream communities, and the ecosystem functions they perform. We expected lower resilience capacity in non-perennial and isolated reaches. Here, we used fish and invertebrate community data and litter decomposition rates across 20 sites in a river network naturally fragmented by drying to characterize the drivers of resilience at the river-network scale. Using discontinuity analysis, a set of resilience indicators were calculated from body size distribution and species traits, and related to flow intermittence, network fragmentation and position in the stream network. We found that non-perennial reaches were characterized by lower resilience with fewer species, lower levels of functional redundancy of five out of eight functional feeding groups. Functional redundancy and response diversity in shredders were decoupled, translating into low litter decomposition rates in non-perennial reaches. Upstream reaches were characterized by low community resilience, likely reflecting their isolated position in the river network, but flow intermittence affected more strongly the resilience of downstream than upstream reaches. Cross-scale functional redundancy and grazer response diversity were driven by network fragmentation, meaning that the functions these groups perform might be at risk when facing other anthropogenic pressures. Finally our study suggests that reliable resilience assessments need to be based on several standardized indicators and call for more studies comparing these indicators in diverse ecosystems.

ecology↗

bioRxiv2025

The Dual Nature of Body-Axis Formation in Hydra Regeneration: Polarity-Morphology Concurrency

The formation of a body-axis is central to animal development and involves both polarity and morphology. While polarity is traditionally associated with biochemical patterning, the morphological aspect of axis formation remains elusive. In regenerating Hydra tissues, we find that morphological evolution in all tissue samples depends on inherited positional information from the donors axis, and a foot precursor emerges early in the process. From the onset of regeneration, the Ca{superscript 2} excitations that drive actomyosin forces for tissue reshaping follow a gradient aligned with the head-foot polarity direction. We conclude that polarity and morphological axis progression occur concurrently through interlinked processes, and that the foot plays a dominant role in this process, a role usually attributed to the head organizer. A simple toy model accounts for the observed regeneration dynamics and illustrates the mechanochemical integration of polarity and morphogenesis. We expect the insights from Hydra to be relevant to broader developmental systems.

biophysics↗

bioRxiv2025

A hermetically closed sample chamber enables time-lapse nano-characterization of pathogenic microorganisms in-vitro

Pathogenic microorganisms, such as pathogenic mycobacteria, pose a global health burden. Studying these organisms is crucial for gaining detailed knowledge about the pathogens and the diseases they cause. To handle pathogenic organisms, specific biosafety measures appropriate to the virulence of the organism must be fulfilled, most importantly ensuring that all manipulations of pathogenic material are performed within a confined environment. Atomic force microscopy (AFM) is a powerful technique to study biological samples at nanometer-scale resolution, yielding also mechanical properties, all while maintaining physiological conditions. However, standard AFM sample holders do not meet stringent biosafety requirements since they do not constitute a confined system. AFM imaging relies on direct contact between the cantilever and the sample and is sensitive to mechanical interference, rendering conventional containment systems for handling infectious substances inapplicable. Here, we introduce a hermetically sealed AFM sample chamber that meets biosafety demands while satisfying the mechanical and optical constraints of correlated optical microscopy and AFM. We imaged various pathogenic mycobacteria to demonstrate the chambers versatility and effectiveness in containing biohazardous materials. This sample chamber enables high-resolution, time-lapse correlated imaging and biomechanical characterization of pathogenic microorganisms in-vitro. It broadens the scope of research with pathogenic microorganisms under safe and controlled conditions.

bioengineering↗

bioRxiv2024

Fluctuation-Driven Morphological Patterning: A Novel Approach to Morphogenesis

Recent experimental investigations into Hydra regeneration revealed a remarkable phenomenon: the morphological transformation of a tissue fragment from the incipient spherical configuration to a tube-like structure - the hallmark of a mature Hydra - has the dynamical characteristics of a first-order phase-transition, with calcium field fluctuations within the tissue playing an essential role. This morphological transition was shown to be generated by activation over an energy barrier within an effective potential that underlies morphogenesis. Inspired by this intriguing insight, we propose a novel mechanism where stochastic fluctuations drive the emergence of morphological patterns. Thus, the inherent fluctuations determine the nature of the dynamics and are not incidental noise in the background of the otherwise deterministic dynamics. Instead, they play an important role as a driving force that defines the attributes of the pattern formation dynamics and the nature of the transition itself. Here, we present a simple model that captures the essence of this novel mechanism for morphological pattern formation. Specifically, we consider a one-dimensional tissue arranged as a closed contour embedded in a two-dimensional space, where the local curvature of the contour is coupled to a non-negative scalar field. An effective temperature parameter regulates the strength of the fluctuations in the system. The tissue exhibits fluctuations near a circular shape at sufficiently low coupling strengths, but as the coupling strength exceeds some critical value, the circular state becomes unstable. The nature of the transition to the new state, namely whether it is a first-order-like or a second-order-like transition, depends on the temperature and the effective cutoff on the wavelength of the spatial variations in the system. It is also found that entropic barriers separate the various metastable states of the system.

biophysics↗

bioRxiv2024

Spatial Dynamics of the Developing Human Heart

Heart development relies on a topologically defined interplay between a diverse array of cardiac cells. We finely curated spatial and single-cell measurements with subcellular imaging-based transcriptomics validation to explore spatial dynamics during early human cardiogenesis. Analyzing almost 80,000 individual cells and 70,000 spatially barcoded tissue regions between the 5.5th and 14th postconceptional weeks, we identified 31 coarse- and 72 fine-grained cell states and mapped them to highly resolved cardiac cellular niches. We provide novel insight into the development of the cardiac pacemaker-conduction system, heart valves, and atrial septum, and decipher heterogeneity of the hitherto elusive cardiac fibroblast population. Furthermore, we describe the formation of cardiac autonomic innervation and present the first spatial account of chromaffin cells in the fetal human heart. We support independent exploration of our datasets by an open-access, spatially centric interactive viewer. In summary, our study delineates the cellular and molecular landscape of the developing hearts architecture, offering links to genetic causes of heart disease.

developmental biology↗

bioRxiv2023

Multi-modal profiling of biostabilized human skin modules reveals a coordinated ecosystem response to injected mRNA-1273 COVID-19 vaccine.

The field of vaccination is witnessing a remarkable surge in the development of innovative strategies. There is a need to develop technological platforms capable of generating human data prior to progressing to clinical trials. Here we introduce VaxSkin, a flexible solution designed for the comprehensive monitoring of the natural human skin ecosystems response to vaccines over time. Based on bioengineering to repurpose surgical resections, it allows a comprehensive analysis of the response to vaccines at both organ and single-cell levels. Upon injection of the mRNA-1273 COVID-19 vaccine, we characterized precise sequential molecular events triggered upon detection of the exogenous substance. We also found that the vaccine consistently targets DC/macrophages and mast cells, regardless of the administration route, while promoting specific cell-cell communications in surrounding immune cell subsets. Given its direct translational relevance, VaxSkin provides a multiscale vision of skin vaccination that could pave the way toward the development of new vaccination development strategies.

bioengineering↗

bioRxiv2023

Hydra morphogenesis as phase-transition dynamics

We utilize whole-body Hydra regeneration from a small tissue segment to develop a physics framework for animal morphogenesis. Introducing experimental controls over this process, an external electric field and a drug that blocks gap junctions, allows us to characterize the essential step in the morphological transition - from a spherical shape to an elongated spheroid. We find that spatial fluctuations of the Ca2+ distribution in the Hydras tissue drive this transition and construct a field-theoretic model that explains the morphological transition as a first-order-like phase transition resulting from the coupling of the Ca2+ field and the tissues local curvature. Various predictions of this model are verified experimentally.

biophysics↗

bioRxiv2023

3-D deconvolution of human skin immune architecture with Multiplex Annotated Tissue Imaging System (MANTIS)

Routine clinical assays, such as conventional immunohistochemistry, often fail to resolve the regional heterogeneity of complex inflammatory skin conditions. Here we introduce MANTIS (Multiplexed Annotated Tissue Imaging System), a flexible analytic pipeline compatible with routine practice, specifically-designed for spatially-resolved immune phenotyping of the skin in experimental or clinical samples. Based on phenotype attribution matrices coupled to -shape algorithms, MANTIS projects a representative digital immune landscape, while enabling automated detection of major inflammatory clusters and concomitant single-cell data quantification of biomarkers. We observed that severe pathological lesions from systemic lupus erythematosus, Kawasaki syndrome or COVID-19-associated skin manifestations share common quantitative immune features, while displaying a non-random distribution of cells with the formation of disease-specific dermal immune structures. Given its accuracy and flexibility, MANTIS is designed to solve the spatial organization of complex immune environments to better apprehend the pathophysiology of skin manifestations.

immunology↗

bioRxiv2022

Comprehensive cell atlas of the first-trimester developing human brain

The adult human brain likely comprises more than a thousand kinds of neurons, and an unknown number of glial cell types, but how cellular diversity arises during early brain development is not known. Here, in order to reveal the precise sequence of events during early brain development, we used single-cell RNA sequencing and spatial transcriptomics to uncover cell states and trajectories in human brains at 5 - 14 post-conceptional weeks (p.c.w.). We identified twelve major classes and over 600 distinct cell states, which mapped to precise spatial anatomical domains at 5 p.c.w. We uncovered detailed differentiation trajectories of the human forebrain, and a surprisingly large number of region-specific glioblasts maturing into distinct pre-astrocytes and pre-oligodendrocyte precursor cells (pre-OPCs). Our findings reveal the emergence of cell types during the critical first trimester of human brain development.

developmental biology↗

bioRxiv2022

Decoding spatiotemporal gene expression of the developing human spinal cord and implications for ependymoma origin

The human spinal cord contains diverse cell types, governed by a series of spatiotemporal events for tissue assembly and functions. However, the spatiotemporal regulation of cell fate specification in the human developing spinal cord remains largely unknown. Single-cell RNA sequencing and spatial transcriptomics techniques have advanced the understanding of human organ development considerably. By performing integrated analysis of single-cell and spatial multi-omics methods, we created a comprehensive developmental cell atlas of the first trimester human spinal cord. Our data revealed that the cell fate commitment of neural progenitor cells and their spatial positioning are spatiotemporally regulated by specific gene sets. Beyond this resource, we unexpectedly discovered unique events in human spinal cord development compared to rodents, including earlier quiescence of active neural stem cells, different regulation of stem cell differentiation, and distinct spatiotemporal genetic regulations of cell fate choices. In addition, using our atlas we identified specific gene expression in cancer stem cells in ependymomas. Thus, we demonstrate spatiotemporal genetic regulation of human spinal cord development as well as its potential to understand novel disease mechanisms and to inspire new therapies.

developmental biology↗

bioRxiv2022

Developmental origins of cell heterogeneity in the human lung

The lung contains numerous specialized cell-types with distinct roles in tissue function and integrity. To clarify the origins and mechanisms generating cell heterogeneity, we created a first comprehensive topographic atlas of early human lung development. We report 83 cell states, several spatially-resolved developmental trajectories and predict cell interactions within defined tissue niches. We integrated scRNA-Seq and spatial transcriptomics into a web-based, open platform for interactive exploration. To illustrate the utility of our approach we show distinct states of secretory and neuroendocrine cells, largely overlapping with the programs activated either during lung fibrosis or small cell lung cancer progression. We define the origin of uncharacterized airway fibroblasts associated with airway smooth muscle in bronchovascular bundles, and describe a trajectory of Schwann cell progenitors to intrinsic parasympathetic neurons controlling bronchoconstriction. Our atlas provides a rich resource for further research and a reference for defining deviations from homeostatic and repair mechanisms leading to pulmonary diseases.

developmental biology↗

bioRxiv2021

Canalized morphogenesis driven by inherited tissue asymmetries in Hydra regeneration

The emergence and stabilization of a body axis is a major step in animal morphogenesis, determining the symmetry of the body plan as well as its polarity. To advance our understanding of the emergence of body-axis polarity we study regenerating Hydra. Axis polarity is strongly memorized in Hydra regeneration even in small tissue segments. What type of processes confer this memory? To gain insight into the emerging polarity, we utilize frustrating initial conditions by studying regenerating tissue strips which fold into hollow spheroids by adhering their distal ends, of opposite original polarities. Despite the convoluted folding process and the tissue rearrangements during regeneration, these tissue strips develop a new organizer in a reproducible location preserving the original polarity and yielding an ordered body plan. These observations suggest that the integration of mechanical and biochemical processes supported by their mutual feedback attracts the tissue dynamics towards a well-defined developmental trajectory biased by weak inherited cues from the parent animal. Hydra thus provide an example of dynamic canalization in which the dynamic rules themselves are inherited, in contrast to the classical picture where a detailed developmental trajectory is pre-determined.

biophysics↗

bioRxiv2021

Calcium fluctuations drive morphological patterning at the onset of Hydra morphogenesis

Understanding how the collective physical processes drive robust morphological transitions in animal development requires the characterization of the relevant fields underlying morphogenesis. Calcium (Ca2+) is known to be such a field. Here we show that the Ca2+ spatial fluctuations, in whole-body Hydra regeneration, exhibit universal properties captured by a field-theoretic model describing fluctuations in a tilted double-well potential. We utilize an external electric field and Heptanol, a drug blocking gap junctions, as two separate controls affecting the Ca2+ activity and pausing the regeneration process in a reversible way. Subjecting the Hydra tissue to an electric field increases the calcium activity and its spatial correlations, while applying Heptanol inhibits the activity and weakens the spatial correlations. The statistical characteristics of the Ca2+ spatial fluctuations - i.e., the coefficient of variation and the skewness - exhibit universal shape distributions across tissue samples and conditions, demonstrating the existence of global constraints over this field. Our analysis shows that the Hydras tissue resides near the onset of bistability; the local Ca2+ activity in different regions fluctuates between low and high excited states. The controls modulate the dynamics near that onset, preserving the universal characteristics of the Ca2+ fluctuations and, by that, maintaining the tissues ability to regenerate.

biophysics↗

bioRxiv2021

Plasticity of body axis polarity in Hydra regeneration under constraints

One of the major events in animal morphogenesis is the emergence of a polar body axis. Here, we combine classic grafting techniques with live imaging to study the emergence of body axis polarity during whole body regeneration in Hydra. Composite tissues are made by fusing two rings, excised from separate animals, in different configurations that vary in the polarity and original positions of the rings along the body axes of the parent animals. Under frustrating initial configurations, body axis polarity that is otherwise stably inherited from the parent animal, can become labile and even be reversed. Importantly, the site of head regeneration exhibits a strong bias toward the edges of the tissue, even when this involves polarity reversal. In particular, we observe head formation at an originally aboral tissue edge, which is not compatible with models of Hydra regeneration based only on preexisting morphogen gradients or an injury response. Rather, we suggest that the structural bias toward head formation at the doublets edge is reinforced by the presence of a defect in the organization of the supra-cellular actin fibers, which invariably forms at the edge as the tissue heals. In this scenario, the defect supports head formation at the edge, even though a defect is neither required nor sufficient for head formation. Altogether, our results suggest that body axis determination is an integrated process that arises from the dynamic interplay between mechanical feedback and signaling processes.

biophysics↗