Biology subjects

Fages, A.

Publications and source records attributed to Fages, A..

5 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

Developmental genetic basis of dorsal spine reduction in acidic-adapted threespine stickleback fish

The repeated emergence of similar phenotypes in independent populations is a widespread feature of evolution, yet the extent to which repeated evolution reflects shared molecular mechanisms, and the factors that determine this similarity, remain unclear. Here, we investigate the genetic basis of dorsal spine reduction in threespine stickleback fish, an adaptive trait that has evolved repeatedly in freshwater populations. Phenotypic analyses of crosses between a spine-reduced population from Scotland and the ancestral marine form reveal a major-effect locus, with the spine-reducing allele acting dominantly and influencing body patterning. Bulk segregant analysis maps this effect to a single region on chromosome VI that overlaps the hoxdb gene cluster. Transcriptomic analyses of larval stages show a gain of hoxdb expression in the developing spine region of spine-reduced fish, consistent with the dominance of the derived allele. Together, these results indicate dorsal spine reduction in threespine stickleback through cis-regulatory changes at hoxdb, a mechanism found to mediate dorsal spine evolution in a different species of stickleback fish too. These findings highlight the role of hox genes in adaptive divergence between natural populations within a species and provide a clear example of parallel evolution at the molecular level between species.

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

Adaptive cellular evolution in the intestinal tracts of hyperdiverse African cichlid fishes

Adaptations related to how nutrients are acquired and processed play a central role in the colonization of novel ecological niches and, therefore, in organismal diversification. While the evolution of feeding structures has been studied extensively in this context, the nature of dietary adaptations in the digestive tract remains largely unexplored. Here, we investigate the cellular and molecular basis of dietary adaptations in the massive radiation of cichlid fishes in Lake Tanganyika using comprehensive single-cell transcriptomic data derived from the intestines of 24 endemic cichlid species with distinct habitats and diets. We show that, at the cellular level, dietary adaptations are primarily driven by anterior enterocytes, and that both the relative abundance and gene expression profiles of these cells have evolved in response to rapid dietary specializations. These dietary adaptations are driven by rapidly evolving cell population-specific genes, suggesting that alterations in epithelial cell specification programs and molecular makeup promote ecological diversification.

evolutionary biology↗

bioRxiv2024

Distinct Gene Regulatory Dynamics Drive Skeletogenic Cell Fate Convergence During Vertebrate Embryogenesis

Cell type repertoires have expanded extensively in metazoan animals, with some clade-specific cells being paramount to their evolutionary success. A prime example are the skeletogenic cells of vertebrates that form the basis of their developing endoskeletons. Depending on anatomical location, these cells originate from three different embryonic precursor lineages - the neural crest, the somites, and the lateral plate mesoderm - yet they converge developmentally towards similar cellular phenotypes. Furthermore, these lineages have gained skeletogenic competency at distinct timepoints during vertebrate evolution, thus questioning to what extent different parts of the vertebrate skeleton rely on truly homologous cell types. Here, we investigate how lineage-specific molecular properties of the three precursor pools are integrated at the gene regulatory level, to allow for phenotypic convergence towards a skeletogenic cell fate. Using single-cell transcriptomics and chromatin accessibility profiling along the precursor-to-skeletogenic cell continuum, we examine the gene regulatory dynamics associated with this cell fate convergence. We find that distinct transcription factor profiles are inherited from the three precursor states, and that lineage-specific enhancer elements integrate these different inputs at the cis-regulatory level, to execute a core skeletogenic program. We propose a lineage-specific gene regulatory logic for skeletogenic convergence from three embryonic precursor pools. Early skeletal cells in different body parts thus share only a partial deep homology. This regulatory uncoupling may render them amenable to individualized selection, to help to define distinct morphologies and biomaterial properties in the different parts of the vertebrate skeleton.

developmental biology↗