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Biology subjects

Marshall, J.

Publications and source records attributed to Marshall, J..

At least 19 recordsLinked to original sources

Cerclage Wire as an Affordable Alternative for Internal Fixation in Murine Critical Sized Defect Models

Critical sized defects (CSDs) are a serious challenge in orthopedics that require the development of more robust and effective treatments to improve quality of life for patients. Current CSD research is limited by the applicable and affordable animal models available. Mice would be the preferred species as they are cheaply housed and have many transgenic variations readily available; however, their small size makes CSD surgeries difficult and expensive. We propose the use of cerclage wires to achieve internal plate fixation. PEEK plates were secured to the right femur of 26 C57BL/6 mice using four cerclage wires to achieve modified double-loop fixation implemented through bicortical holes and defects were created. 10 received 3mm defects and 6 received 4mm defects that were left empty and were taken out to 20 weeks (Group E3, E4). Another 10 received 3mm defects that were filled with a morselized bone graft and were taken out to 8 weeks (Group G3). Blinded longitudinal x-ray grading by orthopedic surgeons was conducted on the empty defects for plate stability and wire fixation. All samples received microCT analysis at their endpoints. There were no significant differences in plate or wire stability between the empty groups and wire scores worsened negligibly over time. MicroCT analysis further supported wire integration as bone growth directly upon the wires was observed in all samples. The efficacy of this model in achieving non-union when left untreated was also confirmed via microCT. Further, only three mice in group G3 achieved union and two of these unions were not optimal. Our study is the first to successfully show that cerclage wire can be used in a murine CSD model to achieve affordability and clinical relevancy.

bioengineering↗

Targeting UBE3A and downstream estrogen receptor-β signaling to restore oligodendroglial homeostasis in Angelman syndrome

Mutations that reduce UBE3A cause Angelman syndrome (AS), a neurodevelopmental disorder marked by severe developmental delay and neuropsychiatric symptoms. Although UBE3A has been studied primarily in neurons, it is also expressed in the oligodendrocyte lineage, raising the possibility that glial dysfunction contributes to disease phenotypes. Here we identify an intrinsic, UBE3A-dependent mechanism that governs oligodendrocyte precursor cell (OPC) homeostasis, a process necessary for normal myelination. Using human iPSC-derived OPCs, we performed a targeted compound screen and found that loss of UBE3A diminishes estrogen receptor-{beta} (ESR{beta}) signaling, leading to impaired OPC self-renewal. Mechanistically, UBE3A sustains ESR{beta} levels in OPCs and thereby maintains downstream signaling required for OPC proliferation and stable OPC density. To address cell-type specificity and neuron-glia interactions, we combined oligodendrocyte-lineage-restricted Ube3a knockdown in vivo with reductionist iPSC neuron-OPC co-culture assays, which together support an intrinsic requirement for oligodendroglial UBE3A in OPC proliferation and myelination. Pharmacologic activation of ESR{beta} with selective agonists restored OPC self-renewal and myelination deficits in AS patient iPSC-based systems and rescued oligodendroglial and behavioral abnormalities in AS mouse models. Notably, ESR{beta} signaling primarily regulates OPC homeostasis rather than directly driving oligodendrocyte differentiation, pinpointing a stage-specific therapeutic entry point. These findings highlight a tractable oligodendroglial pathway downstream of UBE3A with translational potential for AS. One Sentence SummaryUBE3A regulates oligodendroglial homeostasis for myelination via estrogen receptor-{beta} signaling as a therapeutic target for Angelman syndrome.

neuroscience↗

Tunable DNA Origami Nanosensors for Detection of Multiscale Spatial Ion Concentration Gradients

Ion gradients play a vital role in cellular signaling, mechanobiology, and organ-level homeostasis. Despite their importance, accurately mapping these spatial gradients at biologically relevant length scales remains a challenge due to the limited tunability and spatial resolution of conventional fluorescent sensors. Here, we present a DNA origami-based sensor (NanoDyn) with tunable sensitivity that enables the detection of Na+ ion gradients across micron to millimeter scales. The sensor design leverages programmable DNA base-pairing interactions to control both the detection range and sensitivity of the sensor. Using fluorescence spectroscopy, we show that NanoDyn can exhibit programmable sensing ranges spanning [~]100 - 1675 mM Na+. To validate the ability to quantify ion gradients and investigate its spatial resolution, we use a custom microfluidic gradient generator, showing that NanoDyn can resolve changes in ion gradients across multiple scales and over distances as little as [~]6 {micro}m, which here, is limited by the resolution of the microfluidic device. In highlighting the potential of DNA nanodevices as multiscale tunable ion gradient sensors, together with their biocompatibility, high temporal resolution, and potential for multiplexed functionalization, this work expands on the role that DNA nanodevices can play in spatial sensing to study ion-mediated processes in microenvironments. Overall, this work advances DNA nanotechnology as a versatile foundation for biosensing with capabilities to probe ion-mediated signaling in health and disease.

bioengineering↗

Taming the reference genome jungle: the refget sequence collection standard

Reference genomes are foundational to genomics but suffer from widespread ambiguity and incompatibility due to inconsistent naming, undocumented differences, and lack of formal mechanisms for comparison. To address this, we introduce the GA4GH refget Sequence Collections (seqcol) standard. Refget seqcol is a framework for unambiguous representation, retrieval, and comparison of sequence collections such as reference genomes and transcriptomes. The seqcol standard comprises four components: a structured data schema, a canonical encoding algorithm that produces content-based, globally unique identifiers, a retrieval API, and a comparison protocol. This standard enables precise identification of sequence collections, even across decentralized or private systems, and allows compatibility assessments beyond exact identity, such as order-relaxed matches or shared coordinate systems. We applied the refget seqcol standard to 60 human and 36 mouse reference genomes sourced from major providers. Using digest-based comparisons, we quantified levels of similarity across attributes including sequence names, lengths, coordinate systems, and actual sequence content. Our analysis revealed some consistent subsets of sequences or coordinate systems, as well as substantial incompatibility among references and duplicate references under different names. To support adoption of refget seqcol, we provide a Python package implementing the full standard, a web API, and a comparison interface allowing users to assess local references against a curated database. This work offers a scalable, reproducible solution to the reference genome compatibility crisis, enabling improved transparency, reuse, and integration in genomic analyses. Refget seqcol enhances interoperability across tools and datasets, making genomic research more robust and reproducible.

genomics↗

Epithelial-Immune-Stromal Interactions Define Divergent Repair and Fibrosis Pathways After Acute Kidney Injury in Human Renal Transplants

Acute kidney injury (AKI) is a major cause of early graft dysfunction after kidney transplantation, particularly in recipients of high-risk donor kidneys prone to ischemia-reperfusion injury. However, the cellular mechanisms dictating whether injury resolves or progresses to fibrosis remain unclear. This study combines single-nucleus RNA sequencing and imaging mass cytometry (IMC) analysis of human kidney allograft biopsies collected within eight weeks posttransplant, stratified by long-term functional outcomes. Grafts that recovered function were enriched in regenerative proximal tubular (PT) cells co-expressing PROM1, CD24, and injury markers, consistent with scattered tubular cells (STCs). In contrast, non-recovering grafts contained a unique subpopulation of transitional proximal tubule cells (tPT4) characterized by dedifferentiation, loss of epithelial identity, and acquisition of fibroblast-like features. Fibroblast trajectory analysis revealed a profibrotic lineage, progressing from stromal progenitors to myofibroblasts, exclusive to nonrecovery grafts. Immune profiling showed divergent macrophage (M{Phi}) polarization, with reparative M{Phi}2 cells and regulatory dendritic cell (DC)-like signatures in recovering grafts, versus inflammatory M{Phi}1 and pro-fibrotic DCs in non-recovery. IMC confirmed spatial colocalization of injured tubules, activated fibroblasts, and immune cells in fibrotic regions, validated in an independent cohort. Functional assays demonstrated that ischemic epithelial injury activated monocyte-derived M{Phi}s with mixed inflammatory/reparative profiles and induced fibroblast-related gene expression, while PAX8 knockdown impaired epithelial proliferation and promoted pro-inflammatory signaling. These findings reveal epithelial cell plasticity as a central driver of divergent repair outcomes following renal transplant AKI and highlight epithelial-immune-stromal crosstalk as a therapeutic target to promote recovery and prevent chronic graft injury. One Sentence SummarySingle-cell and spatial mapping of human kidney transplants reveal regenerative and fibrotic cell programs across tubular, immune, and stromal compartments that determine whether acute injury resolves or progresses to chronic allograft injury.

biochemistry↗

Polymorphic tandem repeats shape single-cell gene expression across the immune landscape

Tandem repeats (TRs) - highly polymorphic, repetitive sequences across the human genome - are important regulators of gene expression but remain underexplored due to challenges in accurate genotyping and analysis1. Here, we generate new whole genome and single-cell RNA sequencing from >5.4 million blood-derived cells across 1,925 individuals in two cohorts [Cuomo et al., accompanying manuscript], and perform meta-analysis to characterize the impact of variation in >1.7 million TR loci on immune cell type-specific gene expression. We identify >69,000 single-cell expression TR loci (sc-eTRs), 30.7% of which are specific to one of 28 immune cell types, and reveal dynamic regulatory effects using cell-state inference. Matched single-cell ATAC sequencing profiles from >3.4 million nuclei in 922 individuals [Xue et al., accompanying manuscript]. uncover chromatin accessibility QTLs for nearly one-third of expression-associated TRs, supporting coordinated effects on cis-regulatory architecture. Fine-mapping implicates 1,490 TRs as candidate causal drivers of gene expression in 6.1% of tested genes, and colocalization analyses highlight >200 genes in which TRs likely mediate genetic associations with immune and hematological traits. Together, these results provide a genome-wide, multiomic view of TR-mediated regulation in the human immune system, establishing TRs as key contributors to cell type-specific regulatory variation and complex trait architecture.

genomics↗

Deep-sea fish reveal alternative pathway for vertebrate visual development

Vertebrate vision is accomplished by two phenotypically distinct types of photoreceptors in the retina: the saturation-resistant cones for the detection of bright light and the highly sensitive rods for dim light conditions [1]. The current dogma is that, during development, all vertebrates initially feature a cone-dominated retina, and rods are added later [2, 3]. By studying the ontogeny of vision in three species of deep-sea fishes, we show that their larvae express cone-specific genes in photoreceptors with rod-like morphologies. Through development, these fishes either retain this rod-like cone retina (Maurolicus mucronatus) or switch to a retina with true rod photoreceptors with expression of rod-specific genes and transcription factors (Vinciguerria mabahiss and Benthosema pterotum). In contrast to the larvae of most marine fishes, which inhabit the bright upper layer of the open ocean, the larvae of deep-sea fishes occur deeper, exposing them to a dimmer light environment [4-7]. Spectral maxima predictions from molecular dynamics simulations and environmental light estimations suggest that using transmuted photoreceptors that combine the characteristics of both cones and rods maximises visual performance in these dimmer light conditions. Our findings provide molecular, morphological, and functional evidence for the evolution of an alternative developmental pathway for vertebrate vision.

evolutionary biology↗

Damsels in a hidden colour: development of ultraviolet sensitivity and colour patterns in damselfishes (Pomacentridae)

Damselfishes (Pomacentridae) are widespread and highly abundant on tropical coral reefs. They exhibit diverse body colouration within and between the [~]250 species and across ontogenetic stages. In addition to human visible colours (i.e., 400-700 nm), most adult damselfishes reflect ultraviolet (UV, 300-400 nm) colour patches. UV sensitivity and UV colour signals are essential for feeding and form the basis for a secret communication channel invisible to the many UV-blind predatory fish on the reef; however, how these traits develop across ontogenetic stages, and their distribution across the damselfish family is poorly characterised. Here, we used UV photography, phylogenetic reconstructions of opsin genes, differential gene expression analysis (DGE) of retinal samples, to investigate the development of UV vision and colour patterns in three ontogenetic stages (pre-settlement larval, juvenile, and adult) of eleven damselfish species. Using DGE, we found similar gene expression between juveniles and adults, which strongly differed from larvae. All species and all stages expressed at least one UV-sensitive sws1 opsin gene. However, UV body colour patterns only started to appear at the juvenile stage. Moreover, Pomacentrus species displayed highly complex UV body patterns that were correlated with the expression of two sws1 copies. This could mean that some damselfishes can discriminate colours that change only in their UV component. We demonstrate dramatic shifts in both UV sensitivity and UV colouration across the development stages of damselfish, while highlighting the importance of considering ontogeny when studying the coevolution of visual systems and colour signals.

ecology↗

Peptidomimetic inhibitors targeting TrkB/PSD-95 signaling improves cognition and seizure outcomes in an Angelman Syndrome mouse model

Angelman syndrome (AS) is a rare genetic neurodevelopmental disorder with profoundly debilitating symptoms with no FDA-approved cure or therapeutic. Brain-derived neurotrophic factor (BDNF), and its receptor TrkB, have a well-established role as regulators of synaptic plasticity, dendritic outgrowth, dendritic spine formation and maintenance. Previously, we reported that the association of PSD-95 with TrkB is critical for intact BDNF signaling in the AS mouse model, as illustrated by attenuated PLC{gamma} and PI3K signaling and intact MAPK pathway signaling. These data suggest that drugs tailored to enhance the TrkB-PSD-95 interaction may provide a novel approach for the treatment of AS and a variety of NDDs. To evaluate this critical interaction, we synthesized a class of high-affinity PSD-95 ligands that bind specifically to the PDZ3 domain of PSD-95, denoted as Syn3 peptidomimetic ligands. We evaluated Syn3 and its analog D-Syn3 (engineered using dextrorotary (D)-amino acids) in vivo using the Ube3a exon 2 deletion mouse model of AS. Following systemic administration of Syn3 and D-Syn3, we demonstrated improvement in the seizure domain of AS. Learning and memory using the novel object recognition assay also illustrated improved cognition following Syn3 and D-Syn3, along with restored long-term potentiation. Finally, D-Syn3 treated mice showed a partial rescue in motor learning. Neither Syn3 nor D-Syn3 improved gross exploratory locomotion deficits, nor gait impairments that have been well documented in the AS rodent models. These findings highlight the need for further investigation of this compound class as a potential therapeutic for AS and other genetic NDDs.

neuroscience↗

Behavioural evidence of spectral opponent processing in the visual system of stomatopod crustaceans

Stomatopods, commonly known as mantis shrimps, possess an intricate colour vision with up to 12 photoreceptor classes organised in four specialised ommatidia rows (rows 1-4 in the midband region of the eye) for colour perception. While 2-4 spectral sensitivities suffice for most visual systems, the mechanism behind stomatopods 12-channel colour vision remains unclear. Based on neuroarchitecture, it was initially suggested that rows 1-4 may function as four parallel dichromatic channels allowing fine spectral discrimination and strong colour constancy in narrow spectral zones. Subsequently, unexpectedly low resolution in behavioural experiments indicated that a binning processing system may operate instead of or in addition to the normal opponent processing system, categorising information into separate channels to create an activation pattern for rapid colour recognition. Previous anatomical and behavioural studies have speculated on the potential coexistence of these two systems in stomatopods colour vision. However, no behavioural study has specifically investigated the potential for colour opponency in their colour vision. Our findings provide the first direct behavioural evidence for spectral opponency in stomatopods visual system, showing that rows 1-4 operate, at least some of the time, as multiple dichromatic channels.

neuroscience↗

Advancing Tolerogenic Immunotherapy: A Multi-Epitope Vaccine Design Targeting the CYP2D6 Autoantigen in Autoimmune Hepatitis Through Immuno-Informatics

Juvenile autoimmune hepatitis (JAIH) is a rare autoimmune disorder affecting children, characterized by the immune systems misguided attack on liver cells, primarily targeting the CYP2D6 autoantigen. This repeated attack leads to hepatic inflammation, fibrosis, and eventual liver failure. Current therapeutic strategies predominantly rely on immunosuppressive agents or whole B cell depletion antibodies, which render patients susceptible to infections and cancers. Hence, there is an urgent need for antigen-specific therapies to mitigate the severity of autoimmune hepatitis. Tolerogenic antigens represent a promising avenue in immunotherapy, capable of dampening autoimmunity. Here, we present a novel computationally designed multi-epitope tolerogenic vaccine tailored to target CYP2D6, aimed at inducing tolerogenic dendritic cells (DCs) and halting autoimmune progression in JAIH patients. To validate our approach, we have developed a similar vaccine for testing in mouse models of JAIH. The selected tolerogenic epitopes exhibit antigenicity without allergenicity or toxicity, and specifically induce IL-10 production (restricted to CD4+ T cell epitopes). In our vaccine design, tolerogenic poly-epitopes are linked with Toll-like receptor (TLR)-4-agonist, the 50S ribosomal unit, and IL-10, effectively programming DCs towards a tolerogenic state. Molecular docking and dynamic simulations have confirmed strong binding affinities and stable complexes between the vaccine structures, TLR4 and IL-10 receptor alpha (IL-10RA), indicating their potential for in vivo DC interaction and programming. Consequently, this innovative vaccine approach demands further exploration through wet lab experiments to assess its tolerogenicity, safety, and efficacy, thereby laying the groundwork for potential application in clinical settings.

immunology↗

Caveolin-1 Autonomously Regulates Hippocampal Neurogenesis Via Mitochondrial Dynamics

Hippocampal neurogenesis plays instrumental roles in learning and memory. However, the mechanisms underlying neurogenesis are not fully understood. Here we show that the expression of Caveolin-1 (Cav-1), the principal component of caveolae, peaks in neural progenitor cells (NPCs) during neurogenesis. Using NestinCreERT2;Cav-1fl/fl male mice, and CRISPR-sham (Cav-1 Ctrl) and CRISPR/Cas9-edited (Cav-1 KO) human induced-pluripotent stem cells, we observed that Cav-1 deletion led to reduced stem cell proliferation and enhanced differentiation into neurons. This was manifested by increased neuronal dendritic tree surface area and enhanced mouse performance in contextual discrimination. Proteomic analysis revealed that Cav-1 plays a role in mitochondrial pathways in NPCs. Cav-1 localized to the mitochondria in NPCs and co-immunoprecipitated with mitofusion 2. Mitochondrial morphology was elongated in Cav-1 KO NPCs and the expression of mitofusion 2 was increased in mitochondrial fractions. Restoration of Cav-1 levels rescued elongated mitochondrial morphology and altered neuronal differentiation in Cav-1 KO NPCs. Together, this study identifies Cav-1 as a novel regulator of neurogenesis and -dependent learning and memory. Significance StatementThe hippocampal dentate gyrus (DG) orchestrates adult hippocampal neurogenesis (AHN). The precise mechanisms governing AHN remain elusive. Caveolin-1 regulates neurogenesis through mitochondrial fission-fusion process, suggesting Caveolin-1 as a novel regulator of AHN and underscoring the impact of AHN on cognition.

neuroscience↗

Impact of Infectious Diseases on Wild Bovidae Populations in Thailand: Insights from Population Modelling and Disease Dynamics

The wildlife and livestock interface is vital for wildlife conservation and habitat management. Infectious diseases maintained by domestic species may impact threatened species such as Asian bovids, as they share natural resources and habitats. To predict the population impact of infectious diseases with different traits, we used stochastic mathematical models to simulate the population dynamics 100 times over 100 years for a model gaur (Bos gaurus) population with and without disease. We simulated repeated introductions from a reservoir, such as domestic cattle. We selected six bovine infectious diseases; anthrax, bovine tuberculosis, hemorrhagic septicaemia, lumpy skin disease, foot and mouth disease and brucellosis, all of which have caused outbreaks in wildlife populations. From a starting population of 300, the disease-free population increased by an average of 228% over 100 years. Brucellosis with frequency-dependent transmission showed the highest average population declines (-97%), with population extinction occurring 16% of the time. Foot and mouth disease with frequency-dependent transmission showed the lowest impact, with an average population increase of 200%. Overall, acute infections with very high or low fatality had the lowest impact, whereas chronic infections produced the greatest population decline. These results may help disease management and surveillance strategies support wildlife conservation.

ecology↗

Mapping threatened Thai bovids provides opportunities for improved conservation outcomes in Asia

Wild bovids provide important ecosystem functions throughout their ranges. Five wild bovids remain in Thailand: gaur (Bos gaurus), banteng (Bos javanicus), wild water buffalo (Bubalus arnee), mainland serow (Capricornis sumatraensis) and Chinese goral (Naemorhedus griseus). However, their populations and habitats have declined substantially and become fragmented. Here, we identify potentially suitable habitat for these threatened bovids using ecological niche models and quantify how much suitable area remains within protected areas. We combined species occurrence data with environmental variables and used spatially-restricted Biotic-Abiotic-Mobility frameworks with species-specific and single large accessible areas. We used ensembles from eight algorithms for generating maps and out-of-sample predictions to validate model performance against new data. Gaur, banteng, and buffalo models performed well throughout the entire distribution ([≥]62%) and in Thailand ([≥]80%). Mainland serow and Chinese goral performed poorly for the entire distribution and in Thailand, though a 5 km movement buffer markedly improved model performance for serow. Particularly large suitable areas were in Thailand and India for gaur, Cambodia and Thailand for banteng, and India for buffalo. Over 50% of overall suitable habitat is located outside protected areas, with just 9% for buffalo in Thai protected areas, highlighting area for potential habitat management and conflict mitigation.

ecology↗

Structure-based development of new cyclic compoundstargeting PSD-95 PDZ3 domain.

Aberrant BDNF signaling has been proposed to contribute to the pathophysiology of depression and other neurological disorders such as Angelman syndrome. We have previously shown that targeting the TrkB / PSD-95 nexus by peptidomimetic inhibitors is a promising approach for therapeutic intervention. Here we used structure-based knowledge to develop a new peptidomimetic compound series that fuses SynGAP-derived peptides to our prototype compound CN2097. These compounds target the PSD-95 PDZ3 domain and adjoining C helix to achieve bivalent binding that results in up to 7-fold stronger affinity compared to CN2097. These compounds were designed to improve CN2097 specificity for the PDZ3 domain and limited SAR studies have been performed to improve their resistance to proteolysis.

molecular biology↗

B vitamin quantification in lentil seed tissues using ultra-performance liquid chromatography-selected reaction monitoring mass spectrometry

Lentils are an important source of macronutrients, including protein and fiber, as well as micronutrients such as vitamins and minerals, especially in a plant-based diet. Quantifying variation among genotypes, including wild germplasm, is desirable to better understand the genetics of differential B vitamins content for breeding of this trait and to understand their potential contributions to the lentil crop. We analyzed thirty-four cultivated and three wild genotypes for vitamins B1, B2, B3, B5, B6, B7, and B9. Seeds were assayed whole, and separated into cotyledons only, or seed coats only. Variation for all B vitamins was observed across the cultivars. Overall, cotyledons had higher concentrations of B1 and B3, while seed coats had higher concentrations of B2, B5, B6, and B9. Wild accessions had the highest concentrations of vitamin B9 and were also among the highest for vitamin B2. These results demonstrate the differential distribution of B vitamins across seed tissues and lentil genotypes, and that dehulling prior to consumption results in the loss of B vitamins otherwise available in whole seeds. They also indicate there is genetic variability which could be used to increase B-vitamin levels in lentil via breeding.

plant biology↗

Multiple rod layers increase the speed and sensitivity of vision in nocturnal reef fishes

Multibank retinas have rod photoreceptors stacked into multiple layers. They are found in many species of fish that inhabit dim environments and are one of the most common visual adaptations in the deep-sea. Despite its prevalence, the function of multibank retinas remained unknown. Two predominant theories, neither of which has been tested, have emerged: 1) they enhance sensitivity in dim light, and 2) they allow colour vision in dim light. To investigate the sensitivity hypothesis, we performed electrophysiological recordings and compared the rod pigments of three species of nocturnal reef fishes, two with a multibank retina (Neoniphon sammara and Myripristis violacea) and a control species with a single rod bank (Ostorhinchus compressus). Results indicated that nocturnal reef fishes with a multibank retina have higher temporal resolution of vision, as indicated by electrophysiology, and that their rhodopsin proteins likely also have faster retinal release kinetics, as suggested by amino acid substitutions. Electrophysiology also showed that the multibank retina conferred greater sensitivity to both dim and bright intensities than a single rod bank and this occurred at times when rod-derived signals usually dominate the visual response. This study provides the first functional evidence for enhanced dim-light sensitivity using a multibank retina while also suggesting novel roles for the adaptation in enhancing bright-light sensitivity and the speed of vision. SignificanceMost vertebrates have one layer of the dim-light active rod photoreceptors; however, some species have multiple layers, known as a multibank retina. We used electrophysiology on nocturnal reef fishes with and without multibank retinas to evaluate the sensory advantage of having multiple rod layers. We show that fish with multibank retinas have both faster vision and enhanced sensitivity to bright and dim light intensities. Thus, we resolve for the first time the function of multibank retinas - one of the most common visual adaptations in the deep sea. Our findings highlight an unconventional vertebrate visual system as well as the visual capabilities of fishes from the most vast (deep sea) and vibrant (reefs) ecosystems on the planet.

zoology↗

Structural remodeling of peripheral taste neurons is fast and independent of taste cell turnover

Taste bud cells are constantly replaced in taste buds as old cells die and new cells migrate into the bud. The perception of taste relies on new taste bud cells integrating with existing neural circuitry, yet how these new cells connect with a taste ganglion neuron is unknown. Do taste ganglion neurons remodel to accommodate taste bud cell renewal? If so, how much of the taste axon structure is fixed and how much remodels? Here we measured the motility and branching of individual taste arbors (the portion of the axon innervating taste buds) over time with two-photon in vivo microscopy. Terminal branches of taste arbors continuously and rapidly remodel within the taste bud. This remodeling is faster than predicted by taste bud cell renewal, with terminal branches added and lost concurrently. Surprisingly, ablating new taste cells with chemotherapeutic agents revealed that remodeling of the terminal branches of taste arbors does not rely of the renewal of taste bud cells. Although the arbor structure remodeling was fast and intrinsically controlled, no new arbors were added, and few were lost over 100 days. Taste ganglion neurons maintain a stable number of nerve arbors that are each capable of high-speed remodeling. Arbor structural plasticity would permit arbors to locate new taste bud cells, while stability of arbor number could support constancy in the degree of connectivity and function for each neuron over time.

neuroscience↗