Biology subjects

Feuda, R.

Publications and source records attributed to Feuda, R..

18 recordsLinked to original sources

bioRxiv2026

Weckle is a molecular switch that diverts Toll signalling from innate immunity towards growth by engaging Yki

The mechanisms underlying how the brain can switch from a plastic to a degenerative state are unknown. Tolls and Toll-Like receptors (TLRs) could be involved since they underlie both neuroinflammation and structural brain plasticity. Here, we show that the Toll signalling adaptor Weckle (Wek) - a ZAD-Zinc-finger transcription factor - can switch the response from promoting innate immunity or cell death, to inducing growth instead. Myristoylated Wek binds Tolls at the membrane, and concerted PI3K and Toll signalling drive its nuclear translocation. Wek interacts with Yorkie (Yki) - the key regulator of growth restrained by Hippo - enabling its nuclear shuttling. Remarkably, Wek blocks innate immunity. Instead, Wek and Yki together drive glial cell proliferation and growth. Through this mechanism, Toll signalling could promote structural brain plasticity via Wek and Yki downstream. As Tolls and Yki are widespread, these findings could have important implications for understanding also regeneration and cancer.

developmental biology↗

bioRxiv2025

Evolutionarily conserved transcriptional regulators control monoaminergic neuron development

To what extent conserved developmental programs specify homologous cell types is a central question in biology. Here, we address this by focusing on reconstructing monoaminergic neuron development in Drosophila melanogaster embryo using time- resolved single-cell genomics, spatial transcript mapping with hybridisation chain reaction, and targeted metabolomics. We uncover a regulatory landscape in which specific transcription factors are activated before biosynthetic enzymes, establishing a prospective temporal architecture for monoaminergic fate specification. Comparative analyses of developmental single-cell atlases from zebrafish and sea urchin indicate that components of this machinery are conserved across [~]550 million years of bilaterian evolution with orthologous transcription factors showing similar temporal dynamics. Together, these findings point to a putatively conserved regulatory core that interfaces with other context-dependent transcription factors; this interplay accommodates monoaminergic multifunction and subtype diversity across distinct neuroanatomies.

evolutionary biology↗

bioRxiv2025

Monoaminergic neurons share transcriptional identity across Bilaterian animals

The evolutionary conservation of cell types over deep time has long been theorised but remains difficult to demonstrate. Monoaminergic neurons, which produce molecules such as serotonin and dopamine, are central to animal behaviour and cognition, yet their evolutionary origins remain unresolved. Here, we analysed single-cell transcriptomes from 16 metazoan species spanning eight phyla. Using a novel integration method, Orthogroup Recoding, together with experimental validation, we show that monoaminergic neurons form consistent transcriptional clusters across Bilateria. These clusters share a regulatory signature involving conserved transcription factors, including homologues of Fev, Lmx1b, Fer2, Insm, and Isl, suggesting a common regulatory program. This signature extends beyond the brain including other monoaminergic cells, such as the gut enterochromaffin cells and larval sensory neurons. By contrast, non-bilaterian lineages lack the coordinated expression of the transcription factors and the biosynthetic machinery that regulate monoamine production. Our observations support the existence of a shared set of TFs that define monoaminergic identity across in bilaterians.

bioinformatics↗

bioRxiv2025

Molecular characterisation of neurons across animals identify conserved gene expression.

The evolution of the nervous system has been shrouded in controversy since the onset of the genomics era. A large part of this controversy stems from the lack of phylogenetic consensus for the main branches of the animal tree, where often animals with nervous systems do not form a monophyletic group. However, this question can be informed from other non-phylogenetic perspectives, such as comparative genomics. Here we ask how similar are genes differentially expressed in neurons across a representative set of eight animals with a nervous system and tally the presence or absence of their homologs in 10 other animals and two choanoflagellates. We show that proteins from 39 families are differentially expressed in all neurons, regardless of the phylogenetic placement of their lineage, and that the majority of these gene families are present in the (unicellular) closest relatives of animals, choanoflagellates. We found that the members of these 39 gene families are enriched in domains for ion transport and juxtacrine signalling, and that there is one gene family of zinc-dependent extracellular matrix-remodelling proteins which is only found in animals bearing a nervous system. Our results show that common genetic toolkits are in place for the function of nervous systems. We identify a large number of potential new genomic markers linked to the nervous system and hope they can complement ongoing research efforts to better understand this quintessentially animal system.

evolutionary biology↗

bioRxiv2025

A Pre-Bilaterian Origin of Phototransduction Genes and Photoreceptor Cells

The evolution of vision is a major novelty in animals, playing a fundamental role in developing complex behaviours. Vision initiates with a light-triggered phototransduction cascade occurring in photoreceptor cells (PRCs). The two main PRC types, ciliary and rhabdomeric, employ both specific and common genes for phototransduction. Despite being crucial for vision, the origin and evolution of photoreceptor cells and phototransduction pathways remain unclear. Using phylogenetic methods, we studied the evolution of all phototransduction genes, elucidating their gene duplication patterns in over 80 species, including non-bilaterian metazoans and other eukaryotes. Then, we investigated the expression of phototransduction genes in available single-cell RNA-sequencing data from various animals, including non-bilaterians. By using phototransduction genes as markers, we identified putative photoreceptor-like cells across animals and compared their regulatory toolkits. Gene families encoding phototransduction components are generally ancient, predating the origin of vision. However, many phototransduction genes originated in the metazoan stem group. Moreover, putative photoreceptor cells identified in non-bilaterians appeared to express some but not all components of the two well-characterised phototransduction pathways, suggesting potential lineage-specific components involved in phototransduction. Finally, we identified conserved expression of certain transcription factors in putative PRCs in non-bilaterians, suggesting the homology of PRCs.

evolutionary biology↗

bioRxiv2024

An ocean of opsins

In this study, we explored the diversity and evolution of opsins using meta-omic data from the TARA Oceans and TARA Polar Circle expeditions, one of the largest marine datasets available. By using molecular clustering and phylogenetic analyses, we identified and characterized opsins across various taxonomic groups and gene subfamilies. Our results indicate that the majority of opsin sequences belong to arthropods and vertebrates. However, we also detected sequences from all major opsin subfamilies, including r-opsin, c-opsin, xenopsin, and Group-4 opsins. Despite the broad taxonomic scope, no novel opsin gene families were discovered, suggesting a comprehensive understanding of opsin diversity in marine ecosystems. Additionally, we present novel opsin sequences from less-studied taxa, which may serve as a valuable resource for future research into opsin function and diversity.

evolutionary biology↗

bioRxiv2024

Hematophagy generates a convergent genomic signature in mosquitoes and sandflies

Blood-feeding (hematophagy) is widespread across Diptera (true flies), yet the underlying molecular mechanisms remain poorly understood. Using phylogenomics, we show that four gene families associated with neuro-modulation, immune responses, embryonic development, and iron metabolism have undergone independent expansions within mosquitoes and sandflies. Our findings illuminate the underlying genetic basis for blood-feeding adaptations in these important disease vectors.

evolutionary biology↗

bioRxiv2024

Molecular correlates of swarming behaviour in Aedes aegypti males.

Mosquitoes are the deadliest vectors of disease. They impose a huge health burden on human populations spreading parasites as disparate as protozoans (malaria), viruses (yellow fever and more), and nematodes (filariasis), which cause life-threatening conditions. In recent years, mating has been proposed as a putative target for population control. Mosquitoes mate mid-air in swarms initiated by males and triggered by a combination of internal and external stimuli. As the number of females in a swarm is limited, there is intense competition among males. Indeed, males retune their physiology for this demanding behaviour but the underlying genetic changes are largely unknown. Interestingly, recent evidence indicates that the upregulation of circadian clock genes may be involved in the swarming of malaria mosquitoes of the genus Anopheles. Here, we use whole-head RNA-seq to identify gene expression changes in Aedes aegypti males who are engaged in swarming in a laboratory setting. Our results suggest that swarming males tend to lower some housekeeping functions while increasing the remodelling of the cytoskeleton and neuronal connectivity; the transcription of circadian clock genes is unaffected.

genetics↗

bioRxiv2023

The origin, evolution and molecular diversity of the chemokine system

Chemokine signalling performs key functions in cell migration via chemoattraction, such as attracting leukocytes to the site of infection during host defence. The system consists of a ligand, the chemokine, usually secreted outside the cell, and a chemokine receptor on the surface of a target cell that recognises the ligand. Several non-canonical components interact with the system. These include a variety of molecules that usually share some degree of sequence similarity with canonical components and, in some cases, are known to bind to canonical components and/or to modulate cell migration (1, 2). While canonical components have been described in vertebrate lineages, the distribution of the non-canonical components is less clear. Uncertainty over the relationships between canonical and non-canonical components hampers our understanding of the evolution of the system. We used phylogenetic methods, including gene-tree to species-tree reconciliation, to untangle the relationships between canonical and non-canonical components, identify gene duplication events and clarify the origin of the system. We found that unrelated ligand groups independently evolved chemokine-like functions. We found non-canonical ligands outside vertebrates, such as TAFA "chemokines" found in urochordates. In contrast, all receptor groups are vertebrate-specific and all - except ACKR1 - originated from a common ancestor in early vertebrates. Both ligand and receptor copy numbers expanded through gene duplication events at the base of jawed vertebrates, with subsequent waves of innovation occurring in bony fish and mammals.

evolutionary biology↗

bioRxiv2023

Hagfish genome illuminates vertebrate whole genome duplications and their evolutionary consequences

Whole genome duplications (WGDs) are major events that drastically reshape genome architecture and are causally associated with organismal innovations and radiations1. The 2R Hypothesis suggests that two WGD events (1R and 2R) occurred during early vertebrate evolution2, 3. However, the veracity and timing of the 2R event relative to the divergence of gnathostomes (jawed vertebrates) and cyclostomes (jawless hagfishes and lampreys) is unresolved4-6 and whether these WGD events underlie vertebrate phenotypic diversification remains elusive7. Here we present the genome of the inshore hagfish, Eptatretus burgeri. Through comparative analysis with lamprey and gnathostome genomes, we reconstruct the early events in cyclostome genome evolution, leveraging insights into the ancestral vertebrate genome. Genome-wide synteny and phylogenetic analyses support a scenario in which 1R occurred in the vertebrate stem-lineage during the early Cambrian, and the 2R event occurred in the gnathostome stem-lineage in the late Cambrian after its divergence from cyclostomes. We find that the genome of stem-cyclostomes experienced two additional, independent genome duplications (herein CR1 and CR2). Functional genomic and morphospace analyses demonstrate that WGD events generally contribute to developmental evolution with similar changes in the regulatory genome of both vertebrate groups. However, appreciable morphological diversification occurred only after the 2R event, questioning the general expectation that WGDs lead to leaps of morphological complexity7.

genomics↗

bioRxiv2022

Neuromodulation by Monoamines is a Bilaterian Innovation

Monoamines like serotonin, dopamine, and adrenaline/noradrenaline (epinephrine/ norepinephrine) act as neuromodulators that tune the response of the nervous system to the environment with predictable advantages for fitness. For instance, monoamines influence action selection depending on the internal state of the organism, contribute to higher cognitive functions like learning and memory formation and modulate fundamental homeostatic needs such as sleep or feeding. Despite their significance and the extensive research in model organisms, the evolutionary origin of the monoaminergic system is uncertain. Here using a phylogenomic approach we study the evolution of the majority of genes involved in the production, modulation, and detection of monoamines. Our analyses suggest that most of the genes of the monoaminergic system originated in the common ancestor of bilaterians. These findings suggest that the monoaminergic synaptic pathway is a bilaterian innovation. We hypothesise that monoaminergic neuromodulation contributed to the diversification and complexification of behaviour and forms found in Bilateria.

evolutionary biology↗

bioRxiv2022

Duplication and losses of opsin genes in lophotrochozoan evolution

Opsins are G-coupled receptors playing a key role in metazoan visual processes. While many studies enriched our understanding of opsin diversity in several animal clades, the opsin evolution in Lophotrochozoa, one of the major metazoan groups, remains poorly understood. We investigated the opsin evolution in 74 translated lophotrochozoan genomes and capitalized on recently developed phylogenetic approaches. We found that the common ancestor of Lophotrochozoa possessed at least seven opsin paralog groups that underwent divergent evolutionary history in the different phyla. Furthermore, we showed for the first time placopsin-related molecules in Bilateria, that we named pseudopsins, which may prove critical in uncovering opsin evolution.

evolutionary biology↗

bioRxiv2022

Resolving tricky nodes in the tree of life through amino acid recoding

Genomic data allowed for a detailed resolution of the tree of life. Yet, tricky nodes such as the root of the animal, plants, eukaryotes, bacterial and archaeal trees remain unresolved. Genomic datasets are heterogeneous as genes and species evolve under different selective pressures, impending the efficacy of evolutionary analyses. Amino acid recodings were developed to reduce heterogeneity, but clear evidence to justify their use is missing. We use simulated genomic-scale datasets and show that recodings can substantially improve phylogenetic accuracy when tackling tricky nodes. We apply our findings to address the root of the animal tree where the debate centers on whether sponges (Porifera) or comb jellies (Ctenophora) branched out first. We show that results from real data follow predictions from simulated data and indicate that a placement of the ctenophores as the first branching animal lineage is most likely artifactual.

evolutionary biology↗

bioRxiv2021

The temporal dynamics of the sea urchin regulome

In this work, we used Nanostring N-counter technology, to evaluate the mRNA expression level of more than 330 regulatory genes over 34-time points covering the first three days of development of the sea urchin larvae. The hierarchical clustering of the mRNAs expression levels has identified groups corresponding to the major developmental landmarks (e.g., maternal to zygotic transition and gastrulation). Furthermore, comparison with previous experiments indicates high reproducibility of mRNA level temporal dynamics across batches. Finally, we generated an online tool to visualize gene expression during sea urchin larval development. The site can be accessed at https://nanostring2021.herokuapp.com/.

developmental biology↗

bioRxiv2020

The diverging evolutionary history of opsin genes in Diptera

Opsin receptors mediate the visual process in animals and their evolutionary history can provide precious hints on the ecological factors that underpin their diversification. Here we mined the genomes of more than 60 Dipteran species and reconstructed the evolution of their opsin genes in a phylogenetic framework. Our phylogenies indicate that dipterans possess an ancestral set of five core opsins which have undergone several lineage-specific events including an independent expansion of low wavelength opsins in flies and mosquitoes and numerous family specific duplications and losses. Molecular evolutionary studies indicate that gene turnover rate, overall mutation rate, and site-specific selective pressure are higher in Anopheles than in Drosophila; we found signs of positive selection in both lineages, including events possibly associated with their peculiar behaviour. Our findings indicate an extremely variable pattern of opsin evolution in dipterans, showcasing how two similarly aged radiations - Anopheles and Drosophila - can be characterized by contrasting dynamics in the evolution of this gene family.Competing Interest StatementThe authors have declared no competing interest.View Full Text

evolutionary biology↗

bioRxiv2019

Genomic adaptations to aquatic and aerial life in mayflies and the origin of wings in insects

The first winged insects underwent profound morphological and functional transformations leading to the most successful animal radiations in the history of earth. Despite this, we still have a very incomplete picture of the changes in their genomes that underlay this radiation. Mayflies (Ephemeroptera) are one of the extant sister groups of all other winged insects and therefore are at a key phylogenetic position to understand this radiation. Here, we describe the genome of the cosmopolitan mayfly Cloeon dipterum and study its expression along development and in specific organs. We discover an expansion of odorant-binding proteins, some expressed specifically in the breathing gills of aquatic nymphs, suggesting a novel sensory role for gills. In contrast, as flying adults, mayflies make use of an enlarged set of opsins and utilise these visual genes in a sexually dimorphic manner, with some opsins expressed only in males. Finally, to illuminate the origin of wings, we identify a core set of deeply conserved wing-specific genes at the root of the pterygote insects. Globally, this is the first comprehensive study of the structure and expression of the genome of a paleopteran insect and shows how its genome has kept a record of its functional adaptations.

evolutionary biology↗

bioRxiv2019

Profiling cellular diversity in sponges informs animal cell type and nervous system evolution

The evolutionary origin of metazoan cell types such as neurons, muscles, digestive, and immune cells, remains unsolved. Using whole-body single-cell RNA sequencing in a sponge, an animal without nervous system and musculature, we identify 18 distinct cell types comprising four major families. This includes nitric-oxide sensitive contractile cells, digestive cells active in macropinocytosis, and a family of amoeboid-neuroid cells involved in innate immunity. We uncover presynaptic genes in an amoeboid-neuroid cell type, and postsynaptic genes in digestive choanocytes, suggesting asymmetric and targeted communication. Corroborating this, long neurite-like extensions from neuroid cells directly contact and enwrap choanocyte microvillar collars. Our data indicate a link between neuroid and immune functions in sponges, and suggest that a primordial neuro-immune system cleared intruders and controlled ciliary beating for feeding.

developmental biology↗

bioRxiv2019

Ciliary photoreceptors in sea urchin larvae indicate pan-deuterostome cell type conservation

One of the signatures of evolutionarily related cell types is the expression of similar combinations of transcription factors in distantly related animals. Here we present evidence that sea urchin larvae possess bilateral clusters of ciliary photoreceptors that are positioned in the oral/anterior apical neurogenic domain and associated with pigment cells. The expression of synaptotagmin indicates that the photoreceptors are neurons. Immunostaining shows that the sea urchin photoreceptors express an RGR/GO-opsin, opsin3.2, which co-localizes with tubulin on immotile cilia on the cell surface. Furthermore, orthologs of several transcription factors expressed in vertebrate photoreceptors are expressed in sea urchin ciliary photoreceptors, including Otx, Six3, Tbx2/3, and Rx, a transcription factor typically associated with ciliary photoreceptors. Analysis of gene expression during sea urchin development indicates that the photoreceptors derive from the anterior apical neurogenic domain. Thus, based on location, developmental origin, and transcription factor expression, sea urchin ciliary photoreceptors are likely homologous to vertebrate rods and cones. However, we found that genes typically involved in eye development in many animals, including pax6, six1/2, eya, and dac, are not expressed in sea urchin ciliary photoreceptors. Instead, all four genes are co-expressed in the hydropore canal, indicating that these genes operate as a module in an unrelated developmental context. Thus, based on current evidence, we conclude that at least within deuterostomes, ciliary photoreceptors share a common evolutionary origin and express a shared regulatory state that includes Rx, Otx, and Six3, but not transcription factors that are commonly associated with the retinal determination circuit.

developmental biology↗