Biology subjects

Maroudas-Sacks, Y.

Publications and source records attributed to Maroudas-Sacks, Y..

6 recordsLinked to original sources

bioRxiv2025

SpinePy enables automated 3D spatiotemporal quantification of multicellular in vitro systems

Organoids and stem-cell-based embryo models such as gastruloids are powerful systems to quantitatively study morphogenesis and patterning. This requires 3D analysis in reference frames that emerge dynamically over development, but are less stereotypical than in vivo. Meaningful statistical comparison and interpretation of biological and physical quantities in space and time -- such as signaling activity, gene expression or cell flows -- depend on proper quantification in these internal and dynamic coordinate systems, especially in in vitro systems that naturally exhibit larger variation. Here, we present a computational framework, packaged as a modular Python toolkit termed SpinePy, that identifies the emergent primary body axis ("spine") of individual gastruloids and constructs a local, dynamic coordinate system aligned to their morphology. SpinePy enables 3D quantification relative to evolving axes and statistical comparisons of morphodynamics, patterning, and densities across structures with varying geometries. We validate and benchmark SpinePy using both synthetic and experimental gastruloid data, providing practical insights into method performance. Using this framework, we generate 3D patterning maps from gastruloids formed with different initial cell numbers (N0). This reveals distinct patterning classes that are better explained by gastruloid volumes than by N0. While demonstrated in gastruloids, SpinePy is broadly applicable to any multicellular system where analysis relative to evolving internal axes is needed, advancing quantitative and comparative spatial biology.

developmental biology↗

bioRxiv2024

Confinement modulates axial patterning in regenerating Hydra

The establishment of the body plan is a major step in animal morphogenesis. The role of mechanical forces and feedback in patterning the body plan remains unclear. Here we explore this question, by studying regenerating Hydra tissues confined in narrow cylindrical channels which constrain their morphology. We find that frustration between the orientation of the channel and the inherited axis in the regenerating tissues can lead to the formation of a multiaxial body plan. The morphological outcome is directly related to the pattern of nematic topological defects that emerges in the organization of the supracellular actomyosin fibers. When the inherited axis, which can be read out from the initial alignment of the supracellular fibers in the confined spheroid, is parallel to the channels axis, the tissue regenerates normally into animals with a single body axis aligned with the channel. However, regenerating spheroids that are confined in a frustrated perpendicular configuration often develop excess defects (including negatively-charged -[1/2] defects) and regenerate into multiaxial morphologies. The influence of mechanical constraints on the regenerated body plan argues against an axial patterning mechanism that is based solely on inherited gradients of biochemical morphogens. We further show that the dependence of the regeneration outcomes on the initial tissue orientation can be recapitulated by a biophysical model which considers the coupled dynamics of the nematic organization of the actomyosin fibers and a morphogen concentration field, incorporating a mechanochemical feedback loop involving strain-dependent morphogen production at defect sites.

biophysics↗

bioRxiv2024

Mechanical strain focusing at topological defect sites in regenerating Hydra

The formation of a new head during Hydra regeneration involves the establishment of a head organizer that functions as a signaling center and contains an aster-shaped topological defect in the organization of the supracellular actomyosin fibers. Here we show that the future head region in regenerating tissue fragments undergoes multiple instances of extensive stretching and rupture events from the onset of regeneration. These recurring localized tissue deformations arise due to transient contractions of the supracellular ectodermal actomyosin fibers that focus mechanical strain at defect sites. We further show that stabilization of aster-shaped defects is disrupted by perturbations of the Wnt signaling pathway. We propose a closed-loop feedback mechanism promoting head organizer formation, and develop a biophysical model of regenerating Hydra tissues that incorporates a morphogen source activated by mechanical strain and an alignment interaction directing fibers along morphogen gradients. We suggest that this positive feedback loop leads to mechanical strain focusing at defect sites, enhancing local morphogen production and promoting robust organizer formation.

biophysics↗

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

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↗

bioRxiv2020

Topological defects in the nematic order of actin fibers as organization centers of Hydra morphogenesis

Animal morphogenesis arises from the complex interplay between multiple mechanical and biochemical processes with mutual feedback. Developing an effective, coarse-grained description of morphogenesis is essential for understanding how these processes are coordinated across scales to form robust, functional outcomes. Here we show that the nematic order of the supra-cellular actin fibers in regenerating Hydra defines a slowly-varying field, whose dynamics provide an effective description of the morphogenesis process. We show that topological defects in this field, which are long-lived yet display rich dynamics, act as organization centers with morphological features developing at defect sites. These observations suggest that the nematic orientation field can be considered a "mechanical morphogen" whose dynamics, in conjugation with various biochemical and mechanical signaling processes, result in the robust emergence of functional patterns during morphogenesis.

biophysics↗