Biology subjects

Hadjivasiliou, Z.

Publications and source records attributed to Hadjivasiliou, Z..

8 recordsLinked to original sources

bioRxiv2026

Gene Regulatory Networks Mediate Pattern Scaling in Growing Tissues

Developmental patterns can scale with size during growth, a phenomenon commonly attributed to morphogen scaling. Although patterning is orchestrated by gene regulatory networks (GRNs) activated by morphogens, how GRN dynamics interact with growth is not understood. We present a theoretical framework that integrates morphogen signalling, GRN dynamics, and tissue growth. We show that pattern scaling emerges from the interplay of GRN dynamics and growth, even in the absence of morphogen scaling. This relies on memory effects encoded in the GRNs, providing a cell-autonomous route to global scaling, and offering a general mechanism for size-invariant patterning beyond morphogen-based models.

biophysics↗

bioRxiv2026

Meiotic cohesin Rec8 imposes fitness costs on fission yeast gametesfavoring the evolution of parental bias in gene expression

Differences between partner gametes, which evolved repeatedly in eukaryotes, can contribute to the evolution of the sexes, sexual selection and non-Mendelian inheritance1- 4. Yet, the empirical evidence for how functional asymmetries arise between initially equivalent gametes is limited. Here, we combine theoretical and experimental approaches in the fission yeast Schizosaccharomyces pombe to show how selective pressures acting concurrently on gametes and zygotes drive the evolution of gamete differences. We find that despite being morphologically identical, P- and M-type partner gametes invest asymmetrically in zygotic development by contributing different amounts of conserved meiotic cohesins. P-gametes preferentially produce thve Rec85 cohesin that increases zygotic fitness but reduces gamete viability, revealing a trade-off between reproductive success and gamete survival. We demonstrate that this asymmetry is mediated by partner-specific communication and model its evolutionary dynamics using empirically determined parameters. Our results support classical theoretical predictions for the evolution of gamete differences and provide a mechanistic understanding of how molecular asymmetries between partners can originate from opposing selection pressures acting in species that lack morphologically distinct gametes.

evolutionary biology↗

bioRxiv2026

Position Dependent Feedback Drives Scaling and Robustness of Morphogen Gradients

Developmental patterning is remarkably robust to intrinsic and extrinsic variation. Morphogen gradients are a key mechanism driving patterning, and themselves often scale with the size of developing tissues and exhibit robustness to other perturbations. Recent data indicates that expander molecules, thought to drive morphogen scaling through expansion-repression (ER) feedback, have concentration profiles that are position dependent. This challenges the currently accepted ER mechanism that requires uniform expander concentrations and position independent feedback. To reconcile these observations, we introduce a new ER motif that supports morphogen scaling with both uniform and position dependent expander concentrations. We quantify scaling as a function of position, and demonstrate that the spatial profiles of scaling and robustness to perturbations in morphogen production are highly correlated. In contrast to uniform expander concentrations that can confer high levels of scaling and robustness at a single position, position dependent expander concentrations can enhance both scaling and robustness throughout the entire target tissue. We explore trade-offs associated with the dynamic range of the expander concentration, revealing that it can be varied to tune the locations where morphogen gradients confer scaling, robustness and precision simultaneously. These findings offer new insight into how developmental systems balance competing demands to achieve reproducible patterning despite biological variability.

developmental biology↗

bioRxiv2025

Morphogen and juxtacrine signalling dynamically integrate to specify cell fates with single-cell resolution

Morphogen gradients guide tissue patterning but do not act in isolation. How they integrate with other signalling modalities, like juxtacrine signalling, and how these integrations influence pattern resolution and robustness remain unclear. We address this in the Drosophila lamina, where columns of precursors are patterned with single-cell resolution into motion-processing neurons, dependent on a photoreceptor-derived Hedgehog gradient and glial-orchestrated differentiation. Combining experiments and theory, we show that glial-induced ERK activity drives Delta expression in lamina precursors, generating a graded Notch activity pattern. Notch restricts Hedgehog morphogen relay and enhances positional information. Glia act as timekeepers, scheduling ERK-driven differentiation after Hedgehog and Notch patterns are established. Thus, Notch and ERK dynamically integrate with Hedgehog to encode positional information, enabling reproducible cell fate patterning with single-cell resolution.

developmental biology↗

bioRxiv2025

A closed feedback between tissue phase transitions and morphogen gradients drives patterning dynamics

During development mechanochemical cues in the cell microenvironment are translated into signalling to drive cell fate decisions. As cells differentiate collectively, it raises the question of how tissue-level properties affect instructive cues of decision-making. Here, we show that a tissue rigidity phase transition guides patterning by tuning the length-scales and time-scales of morphogen signalling. By combining rigidity percolation theory, reaction-diffusion modelling, quantitative imaging, optogenetics and single-cell transcriptomics in zebrafish, we uncover dynamical global tissue rigidity patterns that actively shape the Nodal morphogen gradient by restricting ligand dispersal and accelerating its signalling activity. In this self-generated mechanism, Nodal, besides driving meso-endoderm fate specification, increases cell-cell adhesion strength via regulating planar cell polarity genes. Once adhesion strength reaches a critical point, it triggers a rigidity transition which collapses tissue porosity. The abrupt tissue reorganisation negatively feeds back on Nodal signalling impacting both its length-scales, by limiting Nodal diffusivity, and its time-scales, by speeding up the expression of its antagonist Lefty, thereby ensuring timely signal termination and robust patterning. Overall, we reveal how emergent properties set the spatiotemporal dynamics of morphogen gradients, uncovering macroscopic mechanisms of pattern formation.

developmental biology↗

bioRxiv2024

Gene network architecture, mutation and selection collectively drive developmental pattern evolvability and predictability

A hallmark of development is the generation of spatial patterns driven by morphogen gradients and Gene Regulatory Networks (GRNs). Although the mechanistic basis by which GRNs orchestrate cellular responses and tissue patterning during development is well understood, their evolutionary dynamics remain less clear. Still, utations in regulatory elements that govern GRN-driven patterning are a key mechanism for patterning evolution. In this study, we use the de novo evolution of a stripe phenotype as a model framework to investigate the evolutionary dynamics associated with the emergence of new spatial gene expression boundaries and the adjustment of existing boundaries. To probe general principles of GRN-driven pattern evolution we introduce a new high-throughput theoretical framework that rapidly produces a comprehensive dataset of evolutionary trajectories. We leverage this large dataset to investigate the types of mutations that drive different phenotypic shifts in spatial patterning. Our findings suggest that the order in which mutations in gene-gene interactions appear, and the specific combination of gene-gene interactions that mutate together determine the evolvability of novel spatial gene expression patterns. We interpret our results in the context of epistatic effects that naturally arise in networks of interconnected genes, and show how contingencies and constraints emerge in our system. Our results elucidate the interplay between mutation and gene network organization, revealing how historical contingencies arise and impact the evolvability of GRNs and the predictability of their evolutionary outcomes.

systems biology↗

bioRxiv2019

Basal protrusions mediate spatiotemporal patterns of spinal neuron differentiation

During early spinal cord development, neurons of particular subtypes differentiate with a sparse periodic pattern while later neurons differentiate in the intervening space to eventually produce continuous columns of similar neurons. The mechanisms that regulate this spatiotemporal pattern are unknown. In vivo imaging of zebrafish reveals differentiating spinal neurons transiently extend two long protrusions along the basal surface of the spinal cord prior to axon initiation. These protrusions express Delta protein consistent with the possibility they influence Notch signalling at a distance of several cell diameters. Experimental reduction of laminin expression leads to smaller protrusions and shorter distances between differentiating neurons. The experimental data and a theoretical model support the proposal that the pattern of neuronal differentiation is regulated by transient basal protrusions that deliver temporally controlled lateral inhibition mediated at a distance. This work uncovers novel, stereotyped protrusive activity of new-born neurons that organizes long distance spatiotemporal patterning of differentiation.

developmental biology↗

bioRxiv2019

Evolution of the mating type locus with suppressed recombination

The two partners required for sexual reproduction are rarely the same. This pattern extends to species which lack sexual dimorphism yet possess self-incompatible gametes determined at mating-type regions of suppressed recombination, likely precursors of sex chromosomes. Here we investigate the role of cellular signaling in the evolution of mating-types. We develop a model of ligand-receptor dynamics within cells, and identify factors that determine the capacity of cells to send and receive signals. The model specifies conditions favoring the evolution of gametes producing ligand and receptor asymmetrically and shows how these are affected by recombination. When the recombination rate can evolve, the conditions favoring asymmetric signaling also favor tight linkage of ligand and receptor loci in distinct linkage groups. These results suggest that selection for asymmetric signaling between gametes was the first step in the evolution of non-recombinant mating-type loci, paving the road for the evolution of anisogamy and sexes.

evolutionary biology↗