Biology subjects

Serra, M.

Publications and source records attributed to Serra, M..

32 records · Page 2Linked to original sources

bioRxiv2024

Sex-specific maladaptive responses to acute stress upon in utero THC exposure are mediated by dopamine

Cannabis remains by far the most consumed illicit drug in Europe. The availability of more potent cannabis has raised concerns regarding the enhanced health risks associated with its use, particularly among pregnant women. Growing evidence shows that cannabis use during pregnancy increases the risks of child psychopathology. We have previously shown that male rat offspring prenatally exposed to {Delta}9-tetrahydrocannabinol (THC), a rat model of prenatal cannabinoid exposure (PCE), display a hyperdopaminergic phenotype associated with a differential susceptibility to acute THC- and stress-mediated effects on sensorimotor gating functions. Here, we explore the contribution of the hypothalamic-pituitary-adrenal (HPA) axis, key regulator of body adaptive stress responses, to the detrimental effects of acute stress on ventral tegmental area (VTA) dopamine neurons and sensorimotor gating function of PCE rats. We report a sex-dependent compromised balance in mRNA levels of genes encoding mineralocorticoid and glucocorticoid receptors in the VTA, alongside with stress-induced pre-pulse inhibition (PPI) deficits. Notably, VTA dopamine neuronal activity is required for the manifestation of stress-dependent deterioration of PPI. Finally, pharmacological manipulations targeting glycogen-synthase-kinase-3-{beta} signaling during postnatal development correct these stress-induced, sex-specific and dopamine-dependent deficits of PPI. Collectively, these results highlight the critical sex-dependent interplay between HPA axis and dopamine system in the regulation of sensorimotor gating functions in rats.

neuroscience↗

bioRxiv2024

Control of Modular Tissue Flows Shaping the Embryo in Avian Gastrulation

Avian gastrulation requires coordinated flows of thousands of cells to form the body plan. We quantified these flows using their fundamental kinematic units: one attractor and two repellers constituting its Dynamic Morphoskeleton (DM). We have also elucidated the mechanistic origin of the attractor, marking the primitive streak (PS), and controlled its shape, inducing gastrulation flows in the chick embryo that are typical of other vertebrates. However, the origins of repellers and dynamic embryo shape remain unclear. Here, we address these questions using active matter physics and experiments. Repeller 1, separating the embryo proper (EP) from extraembryonic (EE) tissues, arises from the tug-of-war between EE epiboly and EP isotropic myosin-induced active stress. Repeller 2, bisecting the anterior and posterior PS and associated with embryo shape change, arises from anisotropic myosin-induced active intercalation in the mesendoderm. Combining mechanical confinement with inhibition of mesendoderm induction, we eliminated either one or both repellers, as predicted by our model. Our results reveal a remarkable modularity of avian gastrulation flows delineated by the DM, uncovering the mechanistic roles of EE epiboly, EP active constriction, mesendoderm intercalation and ingression. These findings offer a new perspective for deconstructing morphogenetic flows, uncovering their modular origin, and aiding synthetic morphogenesis.

developmental biology↗

bioRxiv2024

Control of epiblast cell fate by mechanical cues

In amniotes, embryonic tissues originate from multipotent epiblast cells, arranged in a mosaic of presumptive territories. How these domains fated to specific lineages become segregated during body formation remains poorly understood. Using single cell RNA sequencing analysis and lineage tracing in the chicken embryo, we identify epiblast cells contributing descendants to the neural tube, somites and lateral plate after completion of gastrulation. We show that intercalation after cell division generates important movements of epiblast cells which lead to their relocation to different presumptive territories, explaining this broad spectrum of fates. This tissue remodeling phase is transient, being soon followed by the establishment of boundaries restricting cell movements therefore defining the presumptive territories of the epiblast. Finally, we find that the epiblast faces distinct mechanical constraints along the antero-posterior axis, leading to cell fate alterations when challenged. Together, we demonstrate the critical role of mechanical cues in epiblast fate determination.

developmental biology↗

bioRxiv2024

Accelerated growth increases the somatic epimutation rate in trees

Trees are critical components of ecosystems and of major economic importance. Due to their extraordinary longevity and well-defined modular architecture they have also emerged as model systems to study the long-term accumulation of somatic mutations in plants. Coupled with retrospective life-history and environmental data, trees can offer unique insights into mutational processes that would be difficult to obtain with prospective studies. In addition to genetic mutations, somatic epimutations in the form of stochastic gains and losses of DNA cytosine methylation have been shown to accumulate rapidly during ontogeny. One hypothesis is that somatic epimutations originate from DNA methylation maintenance errors during mitotic cell divisions, which would predict that their rate of accumulation scales with growth rate, rather than with age. Here we test this hypothesis in European beech. We analyzed one of the oldest continuously measured experimental plots in the world. The plot contains an even-aged beech stand that was established in 1822 and monitored for growth at regular intervals until the present. Starting [~]150 years ago, alternative thinning strategies were applied to subplots of this experiment, resulting in differential stem growth rates among trees. We show that accelerated growth significantly increased the per-year somatic epimutation rate at CG dinucleotides, and that this effect is accompanied by differences in cell division rates. Hence, faster growth elevates the chances for methylation maintenance errors during DNA replication per unit time. As somatic CG epimutations can be stably inherited to subsequent generations in plants, our insights have direct ecological and evolutionary implications.

genomics↗

bioRxiv2024

Magnetic Microtweezers for High-Throughput Bioseparation in Sub-Nanoliter Droplets

Multiomics studies at single-cell level require small volume manipulation, high throughput analysis and multiplexed detection, characteristics that droplet microfluidics can tackle. However, the initial step of molecules bioseparation remains challenging. Here, we describe a unique magnetic device to trap and extract magnetic particles in sub-nanoliter droplets, for compartmentalisation of detection steps. Relying on electrodeposition of NiFe structures and microfluidic manipulation, this technology has allowed the purification of genetic material at single-cell scale and was able to reach an extraction rate of 72% for a sample of purified oligonucleotides.

bioengineering↗

bioRxiv2023

Zebrahub - Multimodal Zebrafish Developmental Atlas Reveals the State Transition Dynamics of Late Vertebrate Pluripotent Axial Progenitors

Elucidating the developmental processes of organisms requires a comprehensive understanding of cellular lineages in the spatial, temporal, and molecular domains. In this study, we introduce Zebrahub, a dynamic atlas of zebrafish embryonic development that integrates single-cell sequencing time course data with lineage reconstructions facilitated by light-sheet microscopy. This atlas offers high-resolution and in-depth molecular insights into zebrafish development, achieved through the sequencing of individual embryos across ten developmental stages, complemented by trajectory reconstructions. Zebrahub also incorporates an interactive tool to navigate the complex cellular flows and lineages derived from light-sheet microscopy data, enabling in silico fate mapping experiments. To demonstrate the versatility of our multi-modal resource, we utilize Zebrahub to provide fresh insights into the pluripotency of Neuro-Mesodermal Progenitors (NMPs). Our publicly accessible web-based platform, Zebrahub, is a foundational resource for studying developmental processes at both transcriptional and spatiotemporal levels, providing researchers with an integrated approach to exploring and analyzing the complexities of cellular lineages during zebrafish embryogenesis.

developmental biology↗

bioRxiv2022

Activity-driven extracellular volume expansion drives vertebrate axis elongation

The vertebrate bauplan is primarily established via the formation of embryonic tissues in a head-to-tail progression. The biomechanics of this elongation, which requires the presomitic mesoderm (PSM), remains poorly understood. Here, we find that avian PSM explants can elongate autonomously when physically confined in vitro, producing a pushing force that can largely account for the posterior elongation of the embryo. Tissue elongation results from volumetric expansion that is driven by cellular activity and accompanied by inhomogeneous increase of the extracellular fraction along the AP axis. We show that FGF signaling promotes glycolysis-dependent production of Hyaluronic Acid (HA), which is required for expansion of the posterior PSM. Our findings link body axis elongation to tissue expansion through the metabolic control of extracellular matrix production downstream of FGF signaling. One-Sentence SummaryActive tissue expansion propels body elongation independent of cell proliferation-driven growth

developmental biology↗

bioRxiv2021

A mechanochemical model recapitulates distinct vertebrate gastrulation modes

Gastrulation is a critical event in vertebrate morphogenesis driven by cellular processes, and characterized by coordinated multi-cellular movements that form the robust morphological structures. How these structures emerge in a developing organism and vary across vertebrates remains unclear. Inspired by experiments on the chick, we derive a theoretical framework that couples actomyosin activity to tissue flow, and provides a basis for the dynamics of gastrulation morphologies. Our model predicts the onset and development of observed experimental patterns of wild-type and perturbations of chick gastrulation as a spontaneous instability of a uniform state. Varying the initial conditions and a parameter in our model, allows us to recapitulate the phase space of gastrulation morphologies seen across vertebrates, consistent with experimental observations in the accompanying paper. All together, this suggests that early embryonic self-organization follows from a minimal predictive theory of active mechano-sensitive flows.

developmental biology↗

bioRxiv2021

Reconstruction of distinct vertebrate gastrulation modes via modulation of key cell behaviours in the chick embryo

The morphology of gastrulation driving the internalisation of the mesoderm and endoderm differs dramatically among vertebrate species. It ranges from involution of epithelial sheets of cells through a circular blastopore in amphibians to ingression of mesenchymal cells through a primitive streak in amniotes. By targeting signalling pathways controlling critical cell behaviours in the chick embryo, we generated crescent- and ring-shaped mesendoderm territories in which cells can or cannot ingress. These alterations subvert the formation of the chick primitive streak into the gastrulation modes seen in amphibians, reptiles and teleost fish. Our experimental manipulations are supported by a theoretical framework linking cellular behaviors to self-organized multi-cellular flows in the accompanying paper. All together, this suggests that the evolution of gastrulation movements are largely determined by the shape of and cell behaviours in the mesendoderm territory across different species, and controlled by a relatively small number of signalling pathways.

developmental biology↗

bioRxiv2021

Ageing via sexual perception is a by-product of male adaptive plasticity in Drosophila melanogaster

Sensory perception of environmental cues can dramatically modulate ageing across distant taxa. For example, male Drosophila melanogaster age faster if they perceive female cues but fail to mate (ageing via sexual perception). This finding has been a breakthrough for our understanding of the mechanisms of ageing, yet we ignore how and why such responses have evolved. Here, we used D. melanogaster to ask whether ageing via sexual perception may be a by-product of plastic adaptive responses to female cues, and found that while long-term sexual perception leads to reproductive costs, short-term perception increases male lifetime reproductive success in a competitive environment. Simulations under a wide range of socio-sexual and demographic scenario suggest that such plasticity as a response to sexual perception might be a widespread strategy in nature. Finally, we show that sexual perception can significantly magnify sexual selection (15-27% average increase in the opportunity for selection).

evolutionary biology↗

bioRxiv2021

Cancer-associated fibroblasts actively compress cancer cells and modulate mechanotransduction

During tumor progression, cancer-associated fibroblasts (CAFs) accumulate in tumors and produce excessive extracellular matrix (ECM), forming a capsule that enwraps cancer cells. This capsule is a barrier that restricts tumor growth leading to the buildup of intratumoral pressure. Combining genetic and physical manipulations in vivo with microfabrication and force measurements in vitro, we found that the CAFs capsule is not a passive barrier but instead actively compresses cancer cells using actomyosin contractility. Cancer cells mechanosense CAF compression, resulting in an altered localization of the transcriptional regulator YAP. Abrogation of CAFs contractility in vivo leads to the dissipation of compressive forces and impairment of capsule formation. By mapping CAF force patterns in 3D, we show that compression is a CAF-intrinsic property independent of cancer cell growth. Supracellular coordination of CAFs is achieved through fibronectin cables that serve as scaffolds allowing force transmission. Our study unveils that the contractile capsule actively compresses cancer cells, modulates their mechanical signaling, and reorganizes tumor morphology.

cell biology↗

bioRxiv2020

Body size variability across habitats in the Brachionus plicatilis cryptic species complex

The body size response to temperature is one of the most recognizable but still poorly understood ecological phenomena. Other covarying environmental factors are frequently invoked as either affecting the strength of that response or even driving this pattern. We tested the body size response in five species representing the Brachionus plicatilis cryptic species complex, inhabiting 10 brackish ponds with different environmental characteristics. Principal Component Analysis selected salinity and the oxygen concentration as the most important factors, while temperature and pH were less influential. Path analysis showed a positive interclonal effect of pH on body size. At the interspecific level, the size response was species and factor dependent. Under the lack of a thermos-oxygenic relationship, the expected negative response of size to temperature disappeared, but a positive response of size to oxygen remained. Our results confirm the driving role of oxygen in determining the size-to-temperature patterns observed in the field.

ecology↗

bioRxiv2019

Dynamic Morphoskeletons in Development

Morphogenetic flows in developmental biology are characterized by the coordinated motion of thousands of cells that organize into tissues, naturally raising the question of how this collective organization arises. Using only the Lagrangian kinematics of tissue deformation, which naturally integrates local and global mechanisms along cell paths, we can identifying the Dynamic Morphoskeletons (DM) behind morphogenesis, i.e., the evolving centerpieces of multi-cellular trajectory patterns. The DM is model and parameter-free, frame-invariant, robust to measurement errors, and can be computed from unfiltered cell velocity data. It reveals the spatial attractors and repellers of the embryo, objects that cannot be identified by simple trajectory inspection or Eulerian methods that are local and typically frame-dependent. Computing the DM underlying primitive streak formation in chicken embryo and early gastrulation in the whole fly embryo, we find that the DM captures the early footprint of known morphogenetic features, and reveals new ones, providing a geometric framework to analyze tissue organization.

developmental biology↗

bioRxiv2017

The Population Genomics Of Archaeological Transition In West Iberia

We analyse new genomic data (0.05-2.95x) from 14 ancient individuals from Portugal distributed from the Middle Neolithic (4200-3500 BC) to the Middle Bronze Age (1740-1430 BC) and impute genomewide diploid genotypes in these together with published ancient Eurasians. While discontinuity is evident in the transition to agriculture across the region, sensitive haplotype-based analyses suggest a significant degree of local hunter-gatherer contribution to later Iberian Neolithic populations. A more subtle genetic influx is also apparent in the Bronze Age, detectable from analyses including haplotype sharing with both ancient and modern genomes, D-statistics and Y-chromosome lineages. However, the limited nature of this introgression contrasts with the major Steppe migration turnovers within third Millennium northern Europe and echoes the survival of non-Indo-European language in Iberia. Changes in genomic estimates of individual height across Europe are also associated with these major cultural transitions, and ancestral components continue to correlate with modern differences in stature.\n\nAuthor SummaryRecent ancient DNA work has demonstrated the significant genetic impact of mass migrations from the Steppe into Central and Northern Europe during the transition from the Neolithic to the Bronze Age. In Iberia, archaeological change at the level of material culture and funerary rituals has been reported during this period, however, the genetic impact associated with this cultural transformation has not yet been estimated. In order to investigate this, we sequence Neolithic and Bronze Age samples from Portugal, which we compare to other ancient and present-day individuals. Genome-wide imputation of a large dataset of ancient samples enabled sensitive methods for detecting population structure and selection in ancient samples. We revealed subtle genetic differentiation between the Portuguese Neolithic and Bronze Age samples suggesting a markedly reduced influx in Iberia compared to other European regions. Furthermore, we predict individual height in ancients, suggesting that stature was reduced in the Neolithic and affected by subsequent admixtures. Lastly, we examine signatures of strong selection in important traits and the timing of their origins.

genomics↗