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Bayer, E. A.

Publications and source records attributed to Bayer, E. A..

9 recordsLinked to original sources
bioRxiv2026

Transcriptional subtypes, anatomical organization, and sexual dimorphism of sensory vagus neurons in Danionella cerebrum

Visceral sensory neurons sense and modulate the brain, behavior, and the internal organs. However, these neurons have been difficult to study comprehensively due to their projections deep within the body. Here, we establish the transparent miniature fish Danionella cerebrum as a model for studying the sensory vagus nerve in an adult vertebrate. By generating a transgenic line to label D. cerebrum cranial sensory ganglia, we were able to both anatomically characterize and transcriptionally profile the sensory vagus at single-cell resolution. Anatomically, we find that the vagal ganglia have a somatotopic layout. Transcriptionally, the sensory vagus is comprised of diverse sensory subtypes conserved with other vertebrates, including nutrient-sensing, mechanoreceptive, nociceptive, and thermosensitive subtypes, as well as polymodal combinations. Visualizing subtype marker genes identified somatotopic-specific sensory subtypes. Notably, the D. cerebrum sensory vagus is not static across development: it becomes anatomically sexually dimorphic during sexual maturation and undergoes continuous adult neurogenesis. The molecular and anatomical atlas of the sensory vagus lays the foundation for functional studies of body-brain communication in D. cerebrum.

neuroscience↗
bioRxiv2026

Fertility reversibly modulates C. elegans behavior via gonad-nervous system signaling

While the external cues that generate behavioral responses have been extensively studied, behavioral changes in response to internal stimuli are much less understood. C. elegans hermaphrodites are self-fertile until they exhaust their supply of self-sperm, after which time they can only produce more progeny via mating with a male animal. Fertile hermaphrodites are less likely to be mated by males than sperm-exhausted hermaphrodites. We report that sperm-dependent hermaphrodite escape is facilitated by an aversive response to physical contact (touch stimulus) by males, specifically male turns around the hermaphrodite nose and male contact at the vulva. Using germline masculinizing and feminizing mutants, we found that sperm are both necessary and sufficient to induce contact-dependent mating evasion. Surprisingly, loss of the entire somatic gonad resulted in ectopic evasion behavior, via an oppositional monoaminergic signal. Hermaphrodites lacking the HSN neuron are constitutively receptive to male mating touch both at the vulva and at the nose, suggesting that HSN transmits fertility status to the nervous system. HSN also modulates other downstream circuits, such as the nose touch sensory neurons ASH and FLP, which are required for evasion of male contact at the nose. Taken together, we identified a signaling cascade wherein presence vs. absence of sperm is transmitted via monoaminergic signaling from the somatic gonad to the nervous system. This demonstrates how changes in internal state, such as fertility status, act to modulate neural circuits and alter the valence of sensory input.

neuroscience↗
bioRxiv2025

Spatial constraints drive amylosome-mediated resistant starch degradation by Ruminococcus bromii in the human colon

Degradation of complex dietary fiber by gut microbes is essential for colonic fermentation, short-chain fatty acid production, and microbiome function. Ruminococcus bromii is the primary resistant starch (RS) degrader in humans, which relies on the amylosome, a specialized cell-bound enzymatic complex. To unravel its architecture, function, and the interplay among its components, we applied an holistic multilayered approach and found that amylosome composition RS degradation, and enzymatic synergy are regulated at two levels: structural constraints enforcing enzyme proximity and expression-driven shifts in enzyme proportions. Cryo-electron tomography revealed that the amylosome comprises a constitutive extracellular layer extending toward the RS. However, proteomics demonstrated its remodeling across different growth conditions, with Amy4 and Amy16 comprising 60% of the amylosome in response to RS. Structural and biochemical analyses revealed complementarity and synergistic RS degradation by these enzymes, which allow R. bromii to fine-tune its adaptation to dietary fiber and shape colonic metabolism.

microbiology↗
bioRxiv2025

Integrating bulk and single cell RNA-seq refines transcriptomic profiles of individual C. elegans neurons

Neuron-specific morphology and function are fundamentally tied to differences in gene expression across the nervous system. We previously generated a single cell RNA-seq (scRNA-Seq) dataset for every anatomical neuron class in the C. elegans hermaphrodite. Here we present a complementary set of bulk RNA-seq samples for 52 of the 118 canonical neuron classes in C. elegans. We show that the bulk RNA-seq dataset captures both lowly expressed and noncoding RNAs that are not detected in the scRNA-Seq profile, but also includes false positives due to contamination by other cell types. We present an analytical strategy that integrates the two datasets, preserving both the specificity of scRNA-Seq data and the sensitivity of bulk RNA-Seq. We show that this integrated dataset enhances the sensitivity and accuracy of transcript detection and differential gene analysis. In addition, we show that the bulk RNA-Seq data set detects differentially expressed non-coding RNAs across neuron types, including multiple families of non-polyadenylated transcripts. We propose that our approach provides a new strategy for interrogating gene expression by bridging the gap between bulk and single cell methodologies for transcriptomic studies. We suggest that these datasets advance the goal of delineating the mechanisms that define morphology and connectivity in the nervous system.

genomics↗
bioRxiv2025

The mechanosensory DEG/ENaC channel DEGT-1 is a proprioceptor of C. elegans foregut movement

The gastrointestinal tract is subjected to extensive mechanosensory stimulation during food ingestion. However, the identities of mechanosensory receptors in the enteric nervous system are largely unknown. The pharynx of C. elegans is a structurally and functionally homologous model of the vertebrate foregut, but is comprised of only 20 neurons that are embedded within the muscles and epithelial cells of the organ. Here we report that the DEG/ENaC family ion channel DEGT-1 is a proprioceptor of pharynx movement. DEGT-1 protein is expressed in 4 pharyngeal neurons (MI, M3, I4, and M5) and localized to their neuronal soma in direct contact with the collagenous pharyngeal basement membrane. degt-1 mutants display abnormally rapid feeding in the presence of food, causing global changes in lipid accumulation. degt-1 mutants also pump rapidly when pumping is induced by the presence of serotonin alone, suggesting that DEGT-1 is required for proprioception of pharyngeal pumping itself, rather than sensing ingested food. DEGT-1 is required in only two pharyngeal neurons (I4 and M5) to control pumping rate. Taken together, these results suggest that DEGT-1 modulates pharyngeal pumping rate by relaying proprioceptive feedback generated by the shear force of the pharynx against its own basement membrane. Thus, mechanosensors in enteric nervous systems modulate organ function not only by detecting forces from ingested contents, but also the movements of the organ itself.

neuroscience↗
bioRxiv2024

Understanding the Dynamics of Biomass Deconstruction by the Cellulolytic Anaerobe C. thermocellum

Clostridium thermocellum is one of the most efficient microorganisms for the deconstruction of cellulosic biomass. To achieve this high level of cellulolytic activity, C. thermocellum uses large multienzyme complexes known as cellulosomes to break down complex polysaccharides, notably cellulose, found in plant cell walls. The attachment of bacterial cells to the nearby substrate via the cellulosome has been hypothesized to be the reason for this high efficiency. The region lying between the cell and the substrate has shown great variation and dynamics that are affected by the growth stage of cells and the biomass used for growth. Here, we utilized both photoactivation localization microscopy (PALM) and stochastic optical reconstruction microscopy (STORM) in combination with Density-Based Spatial Clustering of Applications with Noise (DBSCAN) to study the distribution of C. thermocellum cellulosomes at different stages of growth when actively growing on soluble and insoluble substrates, providing a clearer picture of the dynamics of cellulosome populations at the enzyme microbe substrate interface. This research demonstrates the promising application of novel optical methodologies in tandem with targeted mutations within C. thermocellum to test the prevailing theories regarding the mechanisms of cellulosomes and their potential to shuttle onto the biomass for the attachment of C. thermocellum to improve biomass deconstruction.

microbiology↗
bioRxiv2022

Integrating bulk and single cell RNA-seq refines transcriptomic profiles of specific C. elegans neurons.

Neuron-specific morphology and function are fundamentally tied to differences in gene expression across the nervous system. We previously generated a single cell RNA-seq (scRNA-Seq) dataset for every anatomical neuron class in the C. elegans hermaphrodite. Here we present a complementary set of bulk RNA-seq samples for 52 of the 118 canonical neuron classes in C. elegans. We show that the bulk RNA-seq dataset captures both lowly expressed and noncoding RNAs that are not detected in the scRNA-Seq profile, but also includes false positives due to contamination by other cell types. We present an analytical strategy that integrates the two datasets, preserving both the specificity of scRNA-Seq data and the sensitivity of bulk RNA-Seq. We show that this integrated dataset enhances the sensitivity and accuracy of transcript detection and differential gene analysis. In addition, we show that the bulk RNA-Seq data set detects differentially expressed non-coding RNAs across neuron types, including multiple families of non-polyadenylated transcripts. We propose that our approach provides a new strategy for interrogating gene expression by bridging the gap between bulk and single cell methodologies for transcriptomic studies. We suggest that these datasets advance the goal of delineating the mechanisms that define morphology and connectivity in the nervous system.

genetics↗
bioRxiv2021

Nanoscale resolution of microbial fiber degradation in action

Deconstruction of plant cell walls is imperative to global carbon cycling and sustainability efforts. Selected microbes degrade plant fibers using extremely efficient multi-enzymatic cellulosomes assemblies. Organization of cellulosomes on the bacterial cell surface and their ecological regulation remain elusive. By combining structural methodologies with molecular and biochemical approaches on the canonical Clostridium thermocellum system, we provide an unprecedented view into the in-situ structure and distribution of cellulosomal enzymes while interacting with their cellulosic substrate during fiber degradation. Structural exploration of growing cultures revealed isogenic phenotypic heterogeneity of cellulosome organization on single cells across the bacterial population, suggesting a division-of labor strategy driven by product-dependent dynamics. This study demonstrates how structural biology under near-physiological conditions can be employed to develop ecological hypotheses to understand microbial plant-fiber degradation at the single-cell nanoscale level. One Sentence SummaryThis study contributes critical insights into the in-situ organization of cellulosomes and their cellulosic substrates and provides evidence for phenotypic heterogeneity, with dynamic, growth phase-dependent organization of the fiber-degrading machinery.

microbiology↗
bioRxiv2016

Sexually dimorphic differentiation of a C. elegans hub neuron is cell-autonomously controlled by a conserved transcription factor

Functional and anatomical sexual dimorphisms in the brain are either the result of cells that are generated only in one sex, or a manifestation of sex-specific differentiation of neurons present in both sexes. The PHC neurons of the nematode C. elegans differentiate in a strikingly sex-specific manner. While in hermaphrodites the PHC neurons display a canonical pattern of synaptic connectivity similar to that of other sensory neurons, PHC differentiates into a densely connected hub sensory/interneuron in males, integrating a large number of male-specific synaptic inputs and conveying them to both male-specific and sex-shared circuitry. We describe that the differentiation into such a hub neuron involves the sex-specific scaling of several components of the synaptic vesicle machinery, including the vesicular glutamate transporter eat-4/VGLUT, induction of neuropeptide expression, changes in axonal projection morphology and a switch in neuronal function. We demonstrate that these molecular and anatomical remodeling events are controlled cell-autonomously by the phylogenetically conserved Doublesex homolog dmd-3, which is both required and sufficient for sex-specific PHC differentiation. Cellular specificity of dmd-3 action is ensured by its collaboration with non-sex specific terminal selector-type transcription factors whereas sex-specificity of dmd-3 action is ensured by the hermaphrodite-specific master regulator of hermaphroditic cell identity, the Gli-like transcription factor tra-1, which transcriptionally represses dmd-3 in hermaphrodite PHC. Taken together, our studies provide mechanistic insights into how neurons are specified in a sexually dimorphic manner.

neuroscience↗