Biology subjects

Berki, B.

Publications and source records attributed to Berki, B..

6 recordsLinked to original sources

bioRxiv2026

Molecular address codes delineate circuit-specific motor neuron-muscle matchmaking in the developing tetrapod limb

An essential part of nervous systems development is the establishment and refinement of correct circuit architectures. In vertebrate neuromuscular circuits, this requires connecting the axons of motor neurons in the central nervous system to their corresponding muscle groups in the periphery. This process can roughly be sub-divided into two distinct phases: axon guidance towards their innervation territories, followed by the establishment of correct nerve-muscle connections. While the role of attractive and repulsive cues in axon guidance has been studied extensively, relatively little is known about the molecular interactions shaping motor neuron to muscle matchmaking that contribute to circuit specificity and refinement. Here, using the tetrapod limb as a model system, we focus on the maturation of three distinct neuromuscular circuits, targeting different proximal-distal and anterior-posterior territories of the developing chick forelimb, and sequence the transcriptomes of individually backfilled motor neurons as well as of the muscles they connect to. Comparative analyses across circuits suggest the presence of distinct molecular "address codes", based on individual signatures of matching profiles of secreted signaling factors and cell surface receptors. Furthermore, we probe for inherent transcriptional plasticity in this system, using an experimentally altered limb periphery that results in nerve miswiring, and sequence the corresponding motor neuron-muscle pairs. Lastly, to facilitate data exploration, we present an R Shiny app, to investigate circuit-specific ligand-receptor interaction profiles in both neuron-muscle and muscle-neuron directions, in control and experimentally altered limb configurations. Collectively, we present a resource to investigate the cellular and molecular basis for muscle-nerve matching during neuromuscular circuit refinement in the tetrapod limb, with implications for our understanding of vertebrate neuromuscular development and evolution, as well as regenerative approaches targeting re-innervation after injury or nerve damage.

developmental biology↗

bioRxiv2025

The origin and molecular evolution of the mammalian liver cell architecture

The liver is a central organ with essential roles in processes such as nutritional metabolism, detoxification, and immune defense1-6. It has been instrumental in the adaptation of mammalian species to diverse environments, as reflected by its rapid molecular evolution7,8. However, the origins and evolutionary dynamics of liver cell types and their structural organization remain largely unexplored. Here we report evolutionary analyses of transcriptome and chromatin accessibility data for liver cells from 17 species, spanning all major feeding strategies (herbivory, omnivory, carnivory, insectivory), great apes (including humans), placental clades (Afrotheria, Xenarthra, Laurasiatheria, Euarchontoglires), major mammalian lineages (placentals, marsupials, monotremes), and a bird as outgroup. Integrated with spatial transcriptomics, our data reveal that liver zonation--the compartmentalization of hepatocyte functions along the lobule, the livers fundamental anatomical and functional unit--is conserved across mammals but absent in other vertebrates. We find that zonation originated in the mammalian ancestor, driven by the emergence of WNT and R-spondin signaling from central vein endothelial cells, which activate central hepatocyte gene expression via the transcription factor TCF7L2. Despite this conserved architecture and signaling, genes with zonated expression exhibit rapid evolutionary turnover. Consistently, hepatocytes evolve fast, likely due to reduced selective constraints, enabling adaptive changes under positive selection. Alongside immune cells, hepatocytes are therefore key drivers of the livers rapid evolution and functional innovations. In great apes, we identify human-specific shifts in zonation and cell-type-specific expression linked to recent cis-regulatory changes, particularly in genes involved in lipid metabolism, likely contributing to human-specific metabolic traits. Our study uncovers the origins of a mammal-specific liver cell architecture, within which reduced constraints facilitated molecular changes underlying ecological adaptations.

evolutionary biology↗

bioRxiv2025

Transcriptional and cellular maturation of the chick spinal cord in the context of distinct neuromuscular circuits

The chicken spinal cord is a classic model system to study the early specification of neuronal cell types along its anterior-posterior axis. Here, we follow the ensuing maturation dynamics at limb levels with single cell resolution and contrast neuronal populations innervating appendages of distinct form and function. We use gene co-expression modules to identify rare cell populations with specific biological functions, and show that appendages with different motor outputs - wings and legs - rely on largely similar spinal cord cell type repertoires. Challenging the system with experimental alterations to the peripheral limb musculature reveals limited transcriptional changes, but spatially restricted plasticity in spinal cord motor neuron numbers. Collectively, our results provide a resource to investigate the molecular and cellular basis of neuronal maturation in the avian spinal cord and highlight the plastic nature of embryonic cells to adapt to changes in the limb periphery at both developmental and evolutionary timescales. HighlightsO_LICellular and transcriptional maturation of the developing chicken spinal cord at single-cell resolution C_LIO_LISingle-cell weighted gene co-expression network analysis isolates transcriptional maturation dynamics in different neuronal populations C_LIO_LIIn silico identification and in situ verification of novel markers for cerebrospinal fluid-contacting neurons C_LIO_LIMolecular characterization of the avian glycogen body C_LIO_LITranscriptional and compositional changes of spinal cord cell types in the context of different neuromuscular circuits C_LI

developmental biology↗

bioRxiv2024

Developmental origins and evolution of pallial cell types and structures in birds

The advanced cognitive abilities of birds rival those of mammals and have been attributed to evolutionary innovations in the pallium. However, a comprehensive cellular characterization of this brain region in birds has been lacking. We scrutinized the structures, cell types and evolutionary origins of the avian pallium based on single-cell and spatial transcriptomics atlases for the adult and developing chicken, and comparisons to corresponding data from mammals and non-avian reptiles. We found that the avian pallium shares most inhibitory neuron types with other amniotes. While excitatory neuron repertoires in the (medial) hippocampal formation show high conservation, they substantially diverged in other pallial regions during avian evolution, defining novel structures like the avian-specific (dorsal) hyperpallium, whose neuronal gene expression identities partly converge during late development with those of the (ventral) nidopallium. Our work also unveils the evolutionary relationships of pallial structures across amniotes, like the previously unknown homology between avian (lateral) mesopallial and mammalian deep layer cortical neurons. One-Sentence SummaryAn avian neural cell type atlas illuminates the developmental origins and evolution of the amniote pallium.

evolutionary biology↗

bioRxiv2023

TLNRD1 is a CCM complex component and regulates endothelial barrier integrity

We previously identified talin rod domain-containing protein 1 (TLNRD1) as a potent actin-bundling protein in vitro. Here, we report that TLNRD1 is primarily expressed in the vasculature in vivo and that its depletion leads to vascular abnormalities in vivo and loss of barrier integrity in cultured endothelial cells. We demonstrate that TLNRD1 is a component of the cerebral cavernous malformations (CCM) complex through its direct, high-affinity interaction with CCM2. Modeling and functional testing of TLNRD1 and CCM2 mutants reveal that their interaction is mediated by a hydrophobic C-terminal helix in CCM2 that attaches to a hydrophobic groove on the 4-helix domain of TLNRD1. Disruption of this binding interface leads to CCM2 and TLNRD1 accumulation in the nucleus and actin fibers. Notably, a CCM2 pathogenic mutation linked to vascular dementia in patients maps to the interface and disrupts the interaction. Our findings indicate that CCM2 controls TLNRD1 localization to the cytoplasm and inhibits its actin-bundling activity. Based on these results, we propose a new pathway by which the CCM complex modulates the actin cytoskeleton and vascular integrity by controlling TLNRD1 bundling activity.

cell biology↗

bioRxiv2021

Using trait data improves correlation between environment and community data only if abundances are considered

A straightforward way to explore variation between communities is to calculate dissimilarity indices and relate them with environmental and spatial variables. Communities are most often represented by the (relative) abundances of taxa they comprise; however, more recently, the distribution of traits of organisms included in the communities has been shown more strongly related to ecosystem properties. In this study, we test whether taxon- or trait-based dissimilarity is correlated more tightly with environmental difference and geographical distance and how the abundance scale influences this correlation. Our study system is grassland vegetation in Hungary, where we sampled vegetation plots spanning a long productivity gradient from open dry grasslands to marshes in three sites. We considered three traits for vascular plants: canopy height, specific leaf area and seed mass. We obtained field estimates of normalized vegetation difference index (NDVI) as proxy of productivity (water availability) for each plot. We calculated between-community dissimilarities using a taxon-based and a trait-based index, using raw and square-root transformed abundances and presence/absence data. We fitted distance-based redundancy analysis models with NDVI difference and geographical distance on the dissimilarity matrices and evaluated them using variance partitioning. Then, using the pooled data, we calculated non-metric multidimensional scaling ordinations (NMDS) from all types of dissimilarity matrices and made pairwise comparisons using Procrustes analysis. Data analysis was done separately for the three sites. We found that taxonomical dissimilarity matches environmental and spatial variables better when presence/absence data is used instead of abundance. This pattern was mainly determined by the increasing variation explained by space at the presence/absence scale. In contrast to this trend, with trait-based dissimilarity, accounting for abundance increased explained variation significantly due to the higher explanatory power of NDVI. With abundance data, considering traits improved environmental matching to a great extent in comparison with taxonomical information. However, with presence/absence data, traits brought no advantage over taxon-based dissimilarity in any respect. Changing the abundance scale caused larger difference between ordinations in the case of trait-based dissimilarity than with taxonomical dissimilarity. We conclude that considering relevant traits improves environmental matching only if abundances are also accounted for. Supporting informationAdditional graphs supporting the results are presented as appendix. Open researchData used in this research are publicly available from Dryad ###link to be supplied upon acceptance###

ecology↗