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bioRxiv2019

bioRxiv: the preprint server for biology

The traditional publication process delays dissemination of new research, often by months, sometimes by years. Preprint servers decouple dissemination of research papers from their evaluation and certification by journals, allowing researchers to share work immediately, receive feedback from a much larger audience, and provide evidence of productivity long before formal publication. Launched in 2013 as a non-profit community service, the bioRxiv server brought preprinting to the life sciences and recently posted its 310,000th manuscript. The server now receives around ten million views per month and hosts papers spanning all areas of biology. Initially dominated by evolutionary biology, genetics/genomics and computational biology, bioRxiv has been increasingly populated by papers in neuroscience, cell and developmental biology, and many other fields. bioRxiv and its sister server, medRxiv, also played a critical role during the pandemic, rapidly disseminating new discoveries in immunology, virology and epidemiology related to the SARS-CoV-2 virus and its effects. Changes in journal and funder policies that encourage preprint posting helped drive adoption, as did the development of bioRxiv technologies that allow authors to transfer papers easily between bioRxiv and journals. A recent user survey found that 30% of authors post their preprints weeks to months before submitting to a journal whereas 55% post around the time of journal submission. Authors are motivated by a desire to share work early; they value the feedback they receive and very rarely experience any negative consequences of preprint posting. Rapid dissemination via bioRxiv is also encouraging new initiatives that experiment with the peer review process and the development of novel approaches to literature filtering and assessment.

scientific communication and education↗

bioRxiv2026

A developmental chimera: co-option of appendage, secretory and myogenic programs underlies spider venom gland evolution

The evolutionary emergence of complex organs requires the integration of distinct developmental modules, yet the mechanisms bridging divergent tissue programs into unified functional units remain poorly understood. Animal venom systems, combining high-output secretory epithelia with muscular delivery systems, a provide an exceptional model for studying this modular integration. Here, we show that the venom gland of the spider Parasteatoda tepidariorum is a developmental chimera built by the hierarchical co-option of three ancestral programs. The appendage-patterning gene Distal-less establishes the primary spatial coordinate system for gland development. Downstream, the transcription factor sage maintains secretory epithelium identity; its loss causes downregulation of key venom-processing enzymes and triggers a dramatic phenotypic reversion to a neuronal state. This neural upregulation, accompanied by the downregulation of Notch ligands (delta and jagged), reveals that sage actively represses a latent neural program to maintain secretory fate. Crucially, the myogenic factor sum-1 governs the surrounding muscle layer to drive paracrine crosstalk (Wnt) and sustain lipid metabolism. Knockdown of sum-1 downregulates wntless and fatty acid anabolism genes, alongside the abnormal accumulation of lipid droplets in the secretory epithelium. Ultimately, our findings demonstrate how a complex organ is assembled by fusing an appendicular address, a repressed neuroglandular program, and a myogenic metabolic driver. This modular architecture illustrates a fundamental principle in evolutionary developmental biology: novelty can arise by harnessing the physiological and metabolic capacities of adjacent tissues to fuel the physiological demands of a newly emerged organ. Significance statementHow novel organs evolve by integrating distinct developmental modules remains a fundamental question in biology. Using the spider venom gland as a model, we show that this complex organ is a developmental chimera built by recruiting three ancestral tissue programs. The appendage-selector gene Distal-less (Dll) establishes the glands primary proximal-distal structural axis. Downstream, the transcription factor sage maintains secretory epithelial identity by actively repressing a default neural program. Concurrently, the myogenic regulator sum-1 sustains epithelial lipid metabolism through paracrine Wnt signaling. These findings establish a mosaic model of organogenesis, demonstrating that radical evolutionary innovation can arise by forging morphogenetic and metabolic partnerships that harness adjacent tissues to fuel newly emerged structures.

evolutionary biology↗

bioRxiv2023

Three-dimensional fruit growth analysis clarifies developmental mechanisms underlying complex shape diversity in persimmon fruit

How fruit size and shape are determined is of research interest in agriculture and developmental biology. Fruit typically exhibits three-dimensional structures with genotype-dependent geometric features. Although minor developmental variations have been recognized, little research has fully visualized and measured these variations throughout fruit growth. In this study, a high-resolution 3D scanner was used to investigate the fruit development of 51 persimmon (Diospyros kaki) cultivars with various complex shapes. We obtained 2,380 3D fruit models that fully represented fruit appearance, and enabled precise and automated measurements of unique geometric features throughout fruit development. The 3D fruit model analysis identified key stages that determined the shape attributes at maturity. Typically, genetic diversity in vertical groove development was found, and such grooves can be filled by tissue expansion in the carpal fusion zone during fruit development. Furthermore, transcriptome analysis of fruit tissues from groove/non-groove tissues revealed gene co-expression networks that were highly associated with groove depth variation. The presence of YABBY homologs was most closely associated with groove depth and indicated the possibility that this pathway is a key molecular contributor to vertical groove depth variation. These results demonstrate the validity of fruit 3D growth analysis, which is a powerful tool for identifying the developmental mechanisms of fruit shape variation and the molecular basis of this diversity.

plant biology↗

bioRxiv2023

Unraveling cell differentiation mechanisms through topological exploration of single-cell developmental trajectories

Understanding the circuits that control cell differentiation is a fundamental problem in developmental biology. Single-cell RNA sequencing has emerged as a powerful tool for investigating this problem. However, the reconstruction of developmental trajectories is based on the assumption that cell states traverse a tree-like structure, which may bias our understanding of critical developmental mechanisms. To address this limitation, we developed a framework, TopGen, that enables identifying topological signatures of functional biological circuits as persistent homology groups in transcriptome space. First, we show that TopGen can identify genetic drivers of topological structures in simulated datasets. We then applied our approach to more than ten single-cell developmental atlases and found that topological transcriptome spaces are predominantly path-connected and only sometimes simply connected. Finally, we applied TopGen to analyze gene expression patterns in topological loops representing stem-like, transdifferentiation, and convergent cell circuits, found in C. elegans, H. vulgaris, and N. vectensis, respectively. Our results show that some essential differentiation mechanisms use non-trivial topological motifs, and that these motifs can be conserved in a cell-type-specific manner. Thus, our approach to studying the topological properties of developmental transcriptome atlases opens new possibilities for understanding cell development and differentiation.

bioinformatics↗

bioRxiv2026

Microdomes: Micro-engineered Microdome arrays enable standardised and shear-free 3D biology with full-spectrum optical imaging compatibility

Three-dimensional cellular models such as organoids and spheroids hold major promise for developmental biology, disease modelling and precision medicine, yet their large-scale production and analysis remain constrained by handling-induced shear stress, sample fragility, positional instability and limited compatibility with advanced imaging workflows. Here, we introduce Microdomes, dense arrays of open-top, dome-shaped microcavities. Each cavity holds a single specimen in its own miniature aquarium, accessed through a narrow apical opening that admits cells, medium, matrix and staining reagents while shielding it from the shear generated during routine pipetting. Each Microdomes chip accommodates more than 100 spheroids or organoids, supporting diverse cell types, co-culture formats and both matrix-free and matrix-embedded culture. All specimens are retained through prolonged culture, repeated medium exchange, fixation and immunostaining. Because every specimen occupies a fixed, addressable position against a thin transparent film, the same spheroid can be relocated and re-imaged over weeks of culture and across microscopes, from array-wide overviews to subcellular details, without transfer, embedding or other perturbation. Microdomes also support AI-based automated segmentation, from whole-spheroid outlines to individual nuclei in 3D, using common image analysis software. Microdomes thereby turn each array into a self-contained quality control unit, providing specimen-level traceability that organoid production pipelines currently lack.

cell biology↗

bioRxiv2025

Associations between reproduction-focused life strategy, sex and Borderline Personality Disorder symptom expression: Evidence from the NESARC national study.

IntroductionBorderline personality disorder (BPD) features span internalizing and externalizing dimensions of psychopathology, and their expression varies across biological sexes. Despite substantial research efforts, major gaps remain in our understanding of this heterogeneity, particularly regarding its developmental underpinnings. Life history theory, a leading framework in evolutionary developmental biology, can help make sense of this heterogeneity. MethodsIn a large nationally representative prospective survey (n = 34 653), the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), we used Multi-group MIMIC models to investigate whether and how the degree to which individuals trade off somatic maintenance against short-term reproductive goals relates to severity of BPD at a general and a single symptom level, and whether these associations differ between men and women in the general adult population. ResultsMen and women prioritizing short-term reproductive goals over somatic maintenance were more likely to endorse each of the 9 DSM-IV BPD symptoms through higher BPD severity, and were more likely to express impulsivity (b=0.11; SE, 0.018; p<.001) and suicidal/self-mutilation behavior (b =0.24; SE, 0.026; p< .001) and less likely to endorse stress-related paranoid ideation (b=-0.066; SE, 0.023; p=.004). Finally, females with a reproduction-oriented life history strategy were more likely to endorse affective instability than males (Females: b=0.12; SE, 0.025; p<.001; Males: b=-0.015; SE, 0.044; p=0.73). ConclusionsAn evolutionary-developmental framework, rooted in human life history theory can help make sense of the heterogeneous manifestations of BPD. Our work also opens the door for future research on the interplay of the reproduction/maintenance trade-off with other genetic and environmental factors and developmental processes in explaining the occurrence of BPD symptoms.

evolutionary biology↗

bioRxiv2019

Developmental transcriptomes of the sea star, Patiria miniata, illuminate the relationship between conservation of gene expression and morphological conservation

Evolutionary changes in developmental gene expression lead to alteration in the embryonic body plan and biodiversity. A promising approach for linking changes in developmental gene expression to altered morphogenesis is the comparison of developmental transcriptomes of closely related and further diverged species within the same phylum. Here we generated quantitative transcriptomes of the sea star, Patiria miniata (P. miniata) of the echinoderm phylum, at eight embryonic stages. We then compared developmental gene expression between P. miniata and the sea urchin, Paracentrotus lividus (~500 million year divergence) and between Paracentrotus lividus and the sea urchin, Strongylocentrotus purpuratus (~40 million year divergence). We discovered that the interspecies correlations of gene expression level between morphologically equivalent stages decreases with increasing evolutionary distance, and becomes more similar to the correlations between morphologically distinct stages. This trend is observed for different sub-sets of genes, from various functional classes and embryonic territories, but is least severe for developmental genes sub-sets. The interspecies correlation matrices of developmental genes show a consistent peak at the onset of gastrulation, supporting the hourglass model of phylotypic stage conservation. We propose that at large evolutionary distance the conservation of relative expression levels for most sets of genes is more related to the required quantities of transcripts in a cell than to conserved morphogenesis processes. In these distances, the information about morphological similarity is reflected mostly in the interspecies correlations between the expressions of developmental control genes.\n\nAuthor summaryUnderstanding the relationship between the interspecies conservation of gene expression and morphological similarity is a major challenge in modern evolutionary and developmental biology. The Interspecies correlations of gene expression levels have been used extensively to illuminate these relationships and reveal the developmental stages that show the highest conservation of gene expression, focusing on the diagonal elements of the correlation matrices. Here we generated the developmental transcriptomes of the sea star, Patiria miniata, and used them to study the interspecies correlations between closely related and further diverged species within the echinoderm phylum. Our study reveals that the diagonal elements of the correlation matrices contain only partial information. The off-diagonal elements, that compare gene expression between distinct developmental stages, indicate whether the conservation of gene expression is indeed related to similar morphology or instead, to general cellular constraints that linger throughout development. With increasing evolutionary distances the diagonal elements decrease and become similar to the off-diagonal elements, reflecting the shift from morphological to general cellular constraints. Within this trend, the interspecies correlations of developmental control genes maintain their diagonality even at large evolutionary distance, and peak at the onset of gastrulation, supporting the hourglass model of phylotypic stage conservation.

evolutionary biology↗

bioRxiv2025

Inferring the landscapes of mutation and recombination in the common marmoset (Callithrix jacchus) in the presence of twinning and hematopoietic chimerism

The common marmoset (Callithrix jacchus) is an important model in biomedical and clinical research, particularly for the study of age-related, neurodegenerative, and neurodevelopmental disorders (due to their biological similarities with humans), infectious disease (due to their susceptibility to a variety of pathogens), as well as developmental biology (due to their short gestation period relative to many other primates). Yet, while being one of the most commonly used non-human primate models for research, the population genomics of the common marmoset remains relatively poorly characterized, despite the critical importance of this knowledge in many areas of research including genome-wide association studies, models of polygenic risk scores, and scans for the targets of selection. This neglect owes, at least in part, to two biological peculiarities related to the reproductive mode of the species -- frequent twinning and sibling chimerism -- which are likely to affect standard population genetic approaches relying on assumptions underlying the Wright-Fisher model. Using high-quality population genomic data, we here infer the rates and landscapes of mutation and recombination -- two fundamental processes dictating the levels and patterns of genetic variability -- in the presence of these biological features, and discuss our findings in light of recent work in primates. Our results suggest that, while the species exhibits relatively low neutral mutation rates, rates of recombination are in the range of those observed in other anthropoids. Moreover, the recombination landscape of common marmosets, like that of many vertebrates, is dominated by PRDM9-mediated hotspots, with artificial intelligence-based models predicting an intricate 3D-structure of the species-specific PRDM9-DNA binding complex in silico. Apart from providing novel insights into the population genetics of common marmosets, given the importance of the availability of fine-scale maps of mutation and recombination for evolutionary inference, this work will also serve as a valuable resource to aid future genomic research in this widely studied system.

evolutionary biology↗

bioRxiv2017

Forces driving cell sorting in Hydra

Cell sorting, whereby a heterogeneous cell mixture organizes into distinct tissues, is a fundamental patterning process in development. So far, most studies of cell sorting have relied either on 2-dimensional cellular aggregates, in vitro situations that do not have a direct counterpart in vivo, or were focused on the properties of single cells. Here, we report the first multiscale experimental study on 3-dimensional regenerating Hydra aggregates, capable of reforming a full animal. By quantifying the kinematics of single cell and whole aggregate behaviors, we show that no differences in cell motility exist among cell types and that sorting dynamics follow a power law. Moreover, we measure the physical properties of separated tissues and determine their viscosities and surface tensions. Based on our experimental results and numerical simulations, we conclude that tissue interfacial tensions are sufficient to explain Hydra cell sorting. Doing so, we illustrate DArcy Thompsons central idea that biological organization can be understood through physical principles, an idea which is currently re-shaping the field of developmental biology.\n\nSummary statementHydra regenerates after dissociation into single cells. We show how physical mechanisms can explain the first step of regeneration, whereby ectodermal and endodermal cells sort out to form distinct tissue layers.

biophysics↗

bioRxiv2022

A novel mechanism for left-right asymmetry establishment involving tissue remodeling and MyoID

Left-right asymmetries have repeatedly evolved in diverse animals and affect the position, shape or size of specific organs. How novel left-right asymmetries arise remains unknown. Here, we examined Drosophila pachea, where males have evolved unique asymmetric genitalia lobes and a right-sided copulation posture in the past 3-6 million years. We found that male asymmetric lobes grow in pupae during a 360{degrees} clockwise genitalia rotation, a conserved and widespread developmental process in flies. Using two complementary approaches, drug application and a CRISPR-induced MyoID mutant, we altered genitalia rotation and found that asymmetric lobe sizes depend on genitalia rotation completion, while the sidedness of lobe asymmetry is determined by the rotation direction. We then investigated the impact of genital asymmetry on copulation posture. Males with reversed genital asymmetry still mate in the typical right-sided posture, indicating that right-sided behavior is not determined by asymmetric male genitalia. Our study reveals that a novel genitalia asymmetry has evolved through the co-option of a pre-existing tissue remodeling process. Tissue rotation represents a new mechanism, through which a bilateral organ can acquire a left-right size asymmetry. Summary statementHow asymmetric shapes evolve from symmetry is an important question in developmental biology. Using a juvenile hormone derivative, transgenics and CRISPR mutants in the non model species Drosophila pachea, we uncover that the developmental process of male genitalia rotation got co-opted during evolution of D. pachea to determine the extent and direction of a novel genital left-right asymmetry.

evolutionary biology↗

bioRxiv2016

Integrating ecological genomics and eco-evo-devo reveals multiple adaptive peaks in ant populations of the Arizona Sky Islands

Uncovering the genetic basis of adaptation is one of the greatest challenges facing modern evolutionary biology, often sparking much controversy, especially among practitioners within different subfields. Here we ask where is the locus of adaptation from the perspective of ecological genomics (ecogen) and evolutionary developmental biology (evodevo). Ecogen focuses on identifying loci under selection between populations living in different environments by scanning genome-wide patterns of genetic divergence, while evodevo focuses on candidate developmental regulatory genes and networks underlying phenotypic differences between species and higher taxa. We attempt to reconcile these alternative perspectives by studying the response of ant populations to past climate change on the Arizona Sky Islands, which are high elevation mountain ranges that represents a replicated natural experiment. We previously showed that adaptation to climatic changes in the Arizona Sky Islands in ant species Monomorium emersoni occurred through repeatable changes within the gene network underlying the development of dispersal alternative phenotypes: winged and wingless queens. Here, we uncover several loci under positive selection which associate with habitat temperature, a pattern consistent with a predictable and repeated increase in frequency following climatic changes on each of the Sky Islands. Furthermore, we show that gene flow between locations within a Sky Island is not a consequence of dispersal phenotypes and its gene network, but rather, is restricted by temperature adaptation along the ecological gradient. This suggests that the determination of winged and wingless queens may be developmentally plastic, and this plasticity and may facilitate jumps between adaptive peaks on the fitness landscape. This complex interplay promotes predictability on both genetic and phenotypic levels for multiple traits in the same species.

Evolutionary Biology↗

bioRxiv2018

Combination of novel and public RNA-seq datasets to generate an mRNA expression atlas for the domestic chicken

BackgroundThe domestic chicken (Gallus gallus) is widely used as a model in developmental biology and is also an important livestock species. We describe a novel approach to data integration to generate an mRNA expression atlas for the chicken spanning major tissue types and developmental stages, using a diverse range of publicly-archived RNA-seq datasets and new data derived from immune cells and tissues.\n\nResultsRandomly down-sampling RNA-seq datasets to a common depth and quantifying expression against a reference transcriptome using the mRNA quantitation tool Kallisto ensured that disparate datasets explored comparable transcriptomic space. The network analysis tool Miru was used to extract clusters of co-expressed genes from the resulting expression atlas, many of which were tissue or cell-type restricted, contained transcription factors that have previously been implicated in their regulation, or were otherwise associated with biological processes, such as the cell cycle. The atlas provides a resource for the functional annotation of genes that currently have only a locus ID. We cross-referenced the RNA-seq atlas to a publicly available embryonic Cap Analysis of Gene Expression (CAGE) dataset to infer the developmental time course of organ systems, and to identify a signature of the expansion of tissue macrophage populations during development.\n\nConclusionExpression profiles obtained from public RNA-seq datasets - despite being generated by different laboratories using different methodologies - can be made comparable to each other. This meta-analytic approach to RNA-seq can be extended with new datasets from novel tissues, and is applicable to any species.

genomics↗

bioRxiv2022

License to cut: Smart RNA guides for conditional control of CRISPR-Cas9

The Cas9 enzyme is a programmable endonuclease, whose target sequence is directed by a companion RNA guide. Cas9 and RNA guides have revolutionized biology, enabling facile editing of the genome in almost all organisms. Controlling where and when Cas9 and the guide operate is indispensable for many fields ranging from developmental biology to therapeutics, but it remains a challenge. Most methods focus on controlling Cas9 with physico-chemical means (which lack finesse, precision or multiplexing), or transcriptional tools (which are slow and difficult to design). Rather than directly engineering Cas9, engineering the RNA guide itself has emerged as a more general and potent way to manage the activity of Cas9. Here we report smart RNA guides that are conditionally activated by the presence of a specific RNA opener. Contrary to most previous approaches, the design affords ample freedom as spacer and the opener are independent. We demonstrate this flexibility by operating SmartGuides activated by a panel of miRNA relevant for human health, and by composing SmartGuides in Boolean logic circuits. Lastly, we test the SmartGuides in mammalian cells - validating the basics tenets of the design, but also highlighting the challenges that remain to be lifted for in-vivo operation.

bioengineering↗

bioRxiv2024

Harnessing full-text publications for deep insights into C. elegans and Drosophila connectomes

In the rapidly expanding domain of scientific research, tracking and synthesizing information from the rapidly increasing volume of publications pose significant challenges. To address this, we introduce a novel high-throughput pipeline that employs ChatGPT to systematically extract and analyze connectivity information from the full-texts and abstracts of 24,237 and 150,538 research publications concerning Caenorhabditis elegans and Drosophila melanogaster, respectively. This approach has effectively identified 200,219 and 1,194,587 interactions within the C. elegans and Drosophila connectomes, respectively. Utilizing Cytoscape Web, we have developed comprehensive, searchable online connectomes that link relevant keywords to their corresponding PubMed IDs, thus providing seamless access to an extensive knowledge network encompassing C. elegans and Drosophila. Our work highlights the transformative potential of integrating artificial intelligence with bioinformatics to deepen our understanding of complex biological systems. By revealing the intricate web of relationships among key entities in C. elegans and Drosophila, we offer invaluable insights that promise to propel advancements in genetics, developmental biology, neuroscience, longevity, and beyond. We also provide details and discuss significant nodes within both connectomes, including the insulin/IGF-1 signaling (IIS) and the notch pathways. Our innovative methodology sets a robust foundation for future research aimed at unravelling complex biological networks across diverse organisms.

bioinformatics↗

bioRxiv2021

Three-dimensional Multicolor Subcellular Imaging by Fast Serial Sectioning Tomography for Centimeter-scale Specimens

Rapid multicolor three-dimensional (3D) imaging for centimeter-scale specimens with subcellular resolution remains a challenging but captivating scientific pursuit. Here, we present a fast, automated, cost-effective, and versatile multicolor 3D imaging method with ultraviolet (UV) surface excitation and vibratomy-assisted sectioning, termed translational rapid ultraviolet-excited sectioning tomography (TRUST). TRUST enables exogenous molecular-specific fluorescence and endogenous content-rich autofluorescence imaging simultaneously with the help of a UV light-emitting diode and a color camera. Commonly applied tissue preparation procedures (e.g., staining or clearing) are laborious, time-consuming, and may induce detrimental effects on processed samples. In TRUST, formalin-fixed specimens are stained with real-time double labeling layer by layer along with serial widefield optical illumination with raster scanning and mechanical sectioning to improve the staining speed and reveal rich biological information. All vital organs in mice have been imaged by TRUST to demonstrate its fast, robust, and high-content multicolor 3D imaging ability. Moreover, its potential for developmental biology has also been validated by imaging entire mouse embryos (taking [~]2 days for imaging the embryo at the embryonic day of 15). TRUST offers a way for multicontrast and multicolor whole-organ 3D imaging with high resolution and high speed while relieving researchers from heavy sample preparation workload.

bioengineering↗

bioRxiv2026

Purinergic signaling disrupts emergent patterns of multicellular coordination in basal Xenobots.

The ability of self-organizing systems to display emergent, adaptive capabilities is a fundamental feature of biological life. Understanding the mechanisms by which cells co-ordinate at the micro-scale to produce macro-scale structures and behaviors is a fundamental problem in developmental biology. Moreover, it is an important goal of biomedicine to identify triggers that re-wire the physiological patterns of information flow and control signals. Here, we use a recently developed, synthetic biology platform known as basal Xenobots to explore how patterns of information flow and multi-cellular integration are regulated by chemical signaling pathways. Basal Xenobots are modified, organoid-like systems constructed from embryos, and have previously been shown to display complex patterns of information flows. In this study, we recorded calcium signals before and after exposing basal Xenobots to extra-cellular adenosine triphosphate (eATP), and used statistics from multivariate information theory to explore the differences in global patterns of information flow across the cells in each state. We found that eATP resulted in a dramatic reconfiguration of global information processing dynamics, characterized by a global decrease in multi-cellular co-ordination, reduced information transfer and integration, and a decrease in the global entropy rate of the basal Xenobots. These results provide evidence that purinergic signaling may play a key role in the regulation of multi-cellular self-organization, with implications for a variety of clinical disorders thought to involve aberrant purinergic signaling. These results also suggest the possibility that bioengineers may be able to "tune" the degree of self-organizing capacity in living systems via pharmacological intervention.

systems biology↗

bioRxiv2018

Microinjection into the Caenorhabditis elegans embryo using an uncoated glass needle enables cell lineage visualization and reveals cell-non-autonomous adhesion control

Microinjection is a useful method in cell biology, with which exogenous substances are introduced into a cell in a location- and time-specific manner. The Caenorhabditis elegans embryo is an important model system for cell and developmental biology. Applying microinjection to the C. elegans embryo had been difficult due to the rigid eggshell surrounding the embryo. In 2013, microinjection method using a carbon-coated quartz needle for the C. elegans embryo was reported. To prepare the needle, unfortunately, special equipment is required and thus a limited number of researchers can use this method. In this study, we established a method for the microinjection of drugs, dyes, and microbeads into the C. elegans embryo using an uncoated glass needle that can be produced in a general laboratory. This method enabled us to easily detect cell lineage up to adult stages by injecting a fluorescent dye into a blastomere. We also found a cell-non-autonomous control mechanism of cell adhesion; specifically, the injection of an actin inhibitor into one cell at the 2-cell stage enhanced adhesion between daughter cells of the other cell. Our microinjection method is expected to be used for broad studies and could facilitate various discoveries using C. elegans.

cell biology↗

bioRxiv2026

A Novel Network Approach to Identify Sample-Specific Context-Informed Metabolic Signatures During Developmental Processes

Metabolism plays an essential role in cellular processes: development, growth, differentiation, and determination of cell identity. Understanding how metabolic processes dynamically change across cell types, stages, and environmental conditions is crucial for studying developmental biology, aging, and disease progression. Genome-wide metabolic models (GEMs) are a powerful network-based tool for studying these processes by integrating omics data to model context-specific metabolism. However, current approaches, such as Flux Balance Analysis (FBA), have limitations in addressing the dynamic nature of metabolism across developmental stages at a sample-specific resolution. To address this, we introduce a novel network-based method for analyzing cell and stage specific metabolic flow using directed and weighted metabolic networks that account for sample-specific transcriptomic data. We apply this method to study ovarian follicle development, providing a deeper understanding of intra-cellular metabolic processes, identifying key metabolites, enzymes, and potential markers for follicular maturation, important for IVF. By incorporating biologically meaningful data, this approach bridges the gap between theoretical metabolic network models (GEMs) and experimental observations, offering a systems-level view of metabolic dynamics in developmental and understudied contexts.

bioinformatics↗