Biology subjects

Shaw, D.

Publications and source records attributed to Shaw, D..

At least 19 recordsLinked to original sources

bioRxiv2026

Social brain fingerprinting: unique functional connectomes underpin interpersonal behaviours in non-autistic and autistic adults

Human social interaction requires continuous adaptation while preserving stable individual patterns of brain organisation. This study examined whether functional connectome fingerprinting captures person-specific organisation during reciprocal interaction and whether its spatial architecture relates to social role and autistic traits. fMRI data from 70 adults forming 35 dyads were analysed during an iterated Ultimatum Game: 19 non-autistic Proposer-non-autistic Responder dyads and 16 non-autistic Proposer-autistic Responder dyads. Functional connectivity across 400 cortical parcels was used to assess whole-brain identifiability and edge-wise reliability. Connectomes remained identifiable across datasets, roles, and task conditions, with no reduction in global identifiability in mixed dyads. Edge-wise analyses revealed role-related and dataset-dependent differences across distributed large-scale networks. Role-sensitive connectivity features were associated with Autism-Spectrum Quotient scores, supported out-of-sample prediction, and topology-derived features classified AQ-threshold status above chance. Stable connectomic signatures therefore persist during reciprocal interaction while their network organisation varies with social role and autistic traits.

neuroscience↗

bioRxiv2026

The C. elegans nervous system reads the internal state of the hydrogen peroxide-detoxification machinery to trigger escape from this common reactive chemical

Hydrogen peroxide (H2O2) is the most common reactive chemical threat faced by organisms. Here, we map the neural circuit that drives chemotactic escape from environmental H2O2 in the nematode C. elegans. Twenty-four neuron classes with sensory endings at the mouth and nose of the animal detect H2O2. Their response dynamics encode stimulus intensity and exposure history, and their partial redundancy makes avoidance resilient to the loss of individual inputs. Sensing begins when H2O2 oxidizes the peroxidatic and resolving cysteines of the cytosolic peroxiredoxin PRDX-2, which relays this oxidative signal to cysteines on the LITE-1 and GUR-3 ion channels, triggering calcium influx in sensory neurons that drive escape. Most of these neurons release glutamate to drive H2O2-dependent excitation of AIA interneurons, whereas others signal through non-glutamatergic routes, providing multiple routes for signal transmission. Thus, the C. elegans nervous system acts as a hydrogen peroxide sentinel that monitors H2O2-induced changes in the intracellular H2O2-detoxification machinery and relays them to interneurons driving organism-wide escape. This raises the possibility that circuit defects in aging and neurodegenerative disease arise from altered peroxiredoxin-mediated H2O2 signaling rather than primarily from direct macromolecular damage.

neuroscience↗

bioRxiv2025

Relative phase of membrane potential theta oscillations between individual hippocampal neurons code space

The timing of spikes dictates a neurons impact on downstream circuits and behavior, and spike timing is determined by the membrane potential (Vm). However, due to technical challenges, it has been impossible to analyze the relative timing of Vm dynamics between neurons during behavior. Using large scale membrane voltage imaging, we simultaneously recorded Vm from many individual hippocampal neurons in animals engaged in a virtual spatial task. We found that relative phase of Vm theta oscillations across neurons exhibit gradual or discrete shifts depending on spatial position. This finding extends beyond previous studies showing Vm dynamics in single neurons or spiking activity in multiple neurons, revealing previously unknown evidence for consistent coding of space by spike-independent relative phase of Vm theta dynamics between neurons.

neuroscience↗

bioRxiv2025

Modified self-amplifying RNAs mediate robust and prolonged gene expression in the mammalian brain

Facile, non-genomic integrating gene delivery technologies are lacking for rapid onset and prolonged protein expression in the brain. Here we report the protein expression and cell type tropism for an advanced messenger ribonucleic acid (mRNA) technology, modified 5-hydroxymethylcytidine (hm5C) self-amplifying ribonucleic acid (saRNA), when injected into the mouse brain or applied to ex vivo human cortical brain slices. saRNA, encoding fluorescent proteins, encapsulated in an LNP formulation comprising ALC-0315 (present in Comirnaty(R)) efficiently mediates long-lasting protein expression in mouse brain cells beyond five weeks, with detectable expression in some neurons at three months. hm5C saRNA substantially outperforms N1m{Psi} mRNA. In addition to transfecting astrocytes and neurons at the injection site, hm5C saRNA-LNPs label neurons retrogradely. Excitingly, hm5C saRNA-LNPs afford protein expression in human cortical brain slices, with expression emerging within 24 hours and lasting beyond 76 days. Modified saRNA provides new opportunities for mechanistic neuroscience research and therapeutic development.

neuroscience↗

bioRxiv2024

Toward Holistic Solutions to Undernutrition: A Comprehensive Preclinical Protocol for Novel Ready-to-Use Therapeutic Foods Testing

Severe acute malnutrition (SAM) affects over 45 million children under five worldwide. Ready-to-Use Therapeutic Foods (RUTFs), the cornerstone of treatment, reach only 30% of children in need due to high production costs and reliance on imports. RUTF formulations developed from local ingredients have shown varying efficacy levels focusing primarily on weight gain, overlooking critical factors like micronutrient status, skeletal development, and gut health. The presented study establishes a comprehensive protocol for preclinical testing of novel RUTF formulations using a validated juvenile rat model replicating key features of malnutrition in children. Beyond the standard anthropometric measurements (body weight, length, and food consumption), bone quality is assessed through micro-computed tomography and mechanical testing, providing insights into microstructure and functionality beyond standard anthropometric measurements. Concurrently, gut microbiome dynamics are analysed using 16S rRNA sequencing coupled with metabolomic profiling of stool and serum to monitor gut health and systemic recovery.By addressing critical gaps in traditional RUTF evaluations and emphasising locally sourced, cost-effective formulations, this protocol offers a transformative framework for developing accessible and impactful malnutrition treatments. The findings generated through this multidisciplinary approach will guide RUTFs optimisation, strengthen their scientific foundation, and pave the way for evidence-based clinical trials to improve global malnutrition treatment strategies.

physiology↗

bioRxiv2024

Single cell RNA-sequencing reveals no evidence for meiotic sex chromosome inactivation in the threespine stickleback fish

Sex chromosomes often evolve unique patterns of gene expression during spermatogenesis. In many species, sex-linked genes are downregulated during meiosis in response to asynapsis of the heterogametic sex chromosome pair (meiotic sex chromosome inactivation; MSCI). This process has evolved convergently across many taxa with independently derived sex chromosomes. Our understanding how quickly MSCI can evolve and whether it is connected to the degree of sequence degeneration remains limited. Teleost fish are a noteworthy group to investigate MSCI because sex chromosomes have evolved repeatedly across species, often over short evolutionary timescales. Here, we investigate whether MSCI occurs in the threespine stickleback fish (Gasterosteus aculeatus), which have an X and Y chromosome that evolved less than 26 million years ago. Using single-cell RNA-seq, we found that the X and Y chromosomes do not have a signature of MSCI, maintaining gene expression across meiosis. Using immunofluorescence, we also show the threespine stickleback do not form a condensed sex body around the X and Y, a feature of MSCI in many species. We did not see patterns of gene content evolution documented in other species with MSCI. Y-linked ampliconic gene families were expressed across multiple stages of spermatogenesis, rather than being restricted to post-meiotic stages, like in mammals. Our work shows MSCI does not occur in the threespine stickleback fish and has not shaped the evolution of the Y chromosome. In addition, the absence of MSCI in the threespine stickleback suggests this process may not be a conserved feature of teleost fish, despite overall sequence degeneration and structural evolution of the Y chromosome, and argues for additional investigation in other species. We also observed testis-dependent differences in coding and expression evolution for X-linked genes, revealing evidence of testis specific faster- X effect and gene-by-gene dosage compensation. Author SummaryAs male germ cells enter meiosis, the X and Y chromosome of many species undergo a drastic repression of gene expression. In mammals, this process has been shown to be essential for fertility, and the expression of sex-linked genes can lead to meiotic arrest and cell death. This process has only been studied in a handful of organisms, which limits our understanding how extensive MSCI is across the tree of life. Teleost fish are an understudied group with many examples of independently derived sex chromosomes across closely related species. Here, we investigate whether MSCI occurs in the threespine stickleback fish, using single-cell transcriptional profiling. We found gene expression remains active throughout meiosis on the sex chromosomes, indicating MSCI does not occur. This indicates that MSCI is not a conserved feature of all taxa and is not an inevitable outcome of degenerating Y chromosomes.

genetics↗

bioRxiv2024

The importance of small island populations for the long term survival of endangered large-bodied insular mammals

Island populations of large vertebrates have experienced higher extinction rates than mainland populations over long timescales due to demographic stochasticity, genetic drift and inbreeding. Conversely, small island populations often experience relatively less anthropogenic habitat degradation than populations on larger islands, making them potential targets for conservation interventions such as genetic rescue to improve their overall genetic diversity. Here we determine the consequences and conservation implications of long-term isolation and recent human activities on genetic diversity of island populations of two forest-dependent mammals endemic to the Wallacea archipelago: the anoa (Bubalus spp.) and babirusa (Babyrousa spp.). Using genomic analyses and habitat suitability models, we show that, compared to closely related species, populations on mainland Sulawesi exhibit low heterozygosity, high inbreeding, and a high proportion of deleterious alleles. In contrast, populations on smaller islands possess fewer deleterious mutations despite exhibiting lower heterozygosity and higher inbreeding. Site frequency spectra indicate that these patterns reflect stronger, long-term purging in smaller island populations. Our results thus suggest that conservation efforts should focus on protecting small island habitats and avoiding translocations from mainland populations. This study highlights the crucial role of small offshore islands for the long-term survival of Wallaceas iconic and indigenous mammals in the face of development on the mainland. Significance statementWithin tropical archipelagos, such as the Wallacea biodiversity hotspot, larger islands experience greater resource exploitation compared to smaller ones, highlighting the potential of smaller islands as refuges for conservation. To investigate the genetic health of populations on small islands, we used genomic, occurrence, and environmental data from a system of replicated populations of anoa and babirusa across islands of varying sizes. In contrast to larger islands like Sulawesi, our results demonstrate that smaller offshore islands not only provide higher-quality habitats but also support populations that have efficiently purged harmful mutations. Thus, despite their known vulnerability over geological time-frames, small island populations can provide long term insurance against human-driven extinction and conservation efforts should prioritise habitat management over translocations.

evolutionary biology↗

bioRxiv2023

Disruption of myelin structure and oligodendrocyte maturation in a pigtail macaque model of congenital Zika infection

Zika virus (ZikV) infection during pregnancy can cause congenital Zika syndrome (CZS) and neurodevelopmental delay in non-microcephalic infants, of which the pathogenesis remains poorly understood. We utilized an established pigtail macaque maternal-to-fetal ZikV infection/exposure model to study fetal brain pathophysiology of CZS manifesting from ZikV exposure in utero. We found prenatal ZikV exposure led to profound disruption of fetal myelin, with extensive downregulation in gene expression for key components of oligodendrocyte maturation and myelin production. Immunohistochemical analyses revealed marked decreases in myelin basic protein intensity and myelinated fiber density in ZikV-exposed animals. At the ultrastructural level, the myelin sheath in ZikV-exposed animals showed multi-focal decompaction consistent with perturbation or remodeling of previously formed myelin, occurring concomitant with dysregulation of oligodendrocyte gene expression and maturation. These findings define fetal neuropathological profiles of ZikV-linked brain injury underlying CZS resulting from ZikV exposure in utero. Because myelin is critical for cortical development, ZikV-related perturbations in oligodendrocyte function may have long-term consequences on childhood neurodevelopment, even in the absence of overt microcephaly. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=108 SRC="FIGDIR/small/561759v1_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@c0d423org.highwire.dtl.DTLVardef@1a76f40org.highwire.dtl.DTLVardef@178e509org.highwire.dtl.DTLVardef@4d581_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2022

The wild life of ticks: using passive surveillance to determine the distribution and wildlife host range of ticks and the exotic Haemaphysalis longicornis, 2010-2021

BackgroundWe conducted a large-scale, passive regional survey of ticks associated with wildlife of the eastern U.S. Our primary goals were to better assess the current geographic distribution of exotic H. longicornis and to identify potential wild mammalian and avian host species. However, this large-scale survey also provided valuable information regarding the distribution and host associations for many other important tick species that utilize wildlife as hosts. MethodsTicks were opportunistically collected by cooperating state and federal wildlife agencies. All ticks were placed in the supplied vials and host information was recorded, including host species, age, sex, examination date, location (at least county and state), and estimated tick burden were recorded. All ticks were identified to species using morphology, suspect H. longicornis were confirmed through molecular techniques. ResultsIn total, 1,940 hosts were examined from across 369 counties from 23 states in the eastern U.S. From these submissions, 20,626 ticks were collected and identified belonging to 11 different species. Our passive surveillance efforts detected exotic H. longicornis from nine host species from eight states. Notably, some of the earliest detections of H. longicornis in the U.S. were collected from wildlife through this passive surveillance network. In addition, numerous new county reports were generated for Amblyomma americanum, A. maculatum, Dermacentor albipictus, D. variabilis, and Ixodes scapularis. ConclusionsThis study provided data on ticks collected from animals from 23 different states in the eastern U.S. between 2010 - 2021 with the primary goal of better characterizing the distribution and host-associations of the exotic tick H. longicornis; however new distribution data on tick species of veterinary or medical importance was also obtained. Collectively, our passive surveillance has detected numerous new county reports for H. longicornis as well as I. scapularis. Our study utilizing passive wildlife surveillance for ticks across the eastern U.S. is an effective method for surveying a diversity of wildlife host species allowing us to better collect widespread data on current tick distributions relevant to human and animal health.

ecology↗

bioRxiv2022

Single cell transcriptomic profiling of tauopathy in a novel 3D neuron-astrocyte coculture model

The use of iPSC derived brain organoid models to study neurodegenerative disease has been hampered by a lack of systems that accurately and expeditiously recapitulate pathogenesis in the context of neuron-glial interactions. Here we report development of a system, termed AstTau, which propagates toxic human tau oligomers in iPSC derived neuron-astrocyte spheroids. The AstTau system develops much of the neuronal and astrocytic pathology observed in tauopathies including misfolded, phosphorylated, oligomeric, and fibrillar tau, strong neurodegeneration, and reactive astrogliosis. Single cell transcriptomic profiling combined with immunochemistry characterizes a model system that can more closely recapitulate late-stage changes in adult neurodegeneration. The transcriptomic studies demonstrate striking changes in neuroinflammatory and heat shock protein (HSP) chaperone systems in the disease process. Treatment with the HSP90 inhibitor PU-H71 was used to address the putative dysfunctional HSP chaperone system and produced a strong reduction of pathology and neurodegeneration, highlighting the potential of AstTau as a rapid and reproducible tool for drug discovery.

neuroscience↗

bioRxiv2021

Transcriptome profiling of Candidatus Liberibacter asiaticus in citrus and psyllids

Candidatus Liberibacter asiaticus (Las) is an emergent bacterial pathogen that is associated with the devastating citrus Huanglongbing (HLB). Vectored by the Asian citrus psyllid, Las colonizes the phloem tissue of citrus, causing severe damage to infected trees. So far, cultivating pure Las culture in axenic media has not been successful and dual-transcriptome analyses aiming to profile gene expression in both Las and its host(s) have a low coverage of the Las genome due to the low abundance of bacterial RNA in total RNA extracts from infected tissues. Therefore, the lack of a Las transcriptome remains as a significant knowledge gap. Here, we used a bacterial cell enrichment procedure and confidently determined the expression profiles of approximately 84% of the Las genes. Genes that exhibited the highest expression levels in citrus include ion transporters, ferritin, outer membrane porins, and genes involved in phage-related functions, pilus formation, cell wall modification, and stress responses. One hundred and six genes were found to be differentially expressed in citrus vs psyllids. Genes related to transcription/translation and resilience to host defense response were upregulated in citrus; whereas genes involved in energy generation and the flagella system were expressed to higher levels in psyllids. We also determined the relative expression levels of potential Sec-dependent effectors, which are considered as key virulence factors of Las. This work advances our understanding of HLB biology and offers novel insight into the interactions of Las with its plant host and insect vector.

microbiology↗

bioRxiv2021

A two-year study on the phenology, host and habitat associations, and pathogens of Haemaphysalis longicornis in Virginia, U.S.A.

Understanding the abiotic and biotic variables affecting tick populations is essential for studying the biology and health risks associated with vector species. We conducted a study on the phenology of exotic Haemaphysalis longicornis (Asian longhorned tick) at a site in Albemarle County, Virginia. We assessed the importance of available wildlife hosts, habitats, and microclimate variables such as temperature, relative humidity, and wind speed on this exotic ticks presence and abundance. In addition, we determined the prevalence of selected tick-borne pathogens potentially transmitted by H. longicornis. We determined that the seasonal activity of H. longicornis was slightly different from previous studies in the northeastern United States. We observed nymphal ticks persist year-round but were most active in the spring, followed by a peak in adult activity in the summer and larval activity in the fall seasons. We also observed a lower probability of detecting H. longicornis in field habitats and the summer months. In addition, we detected H. longicornis on several wildlife hosts, including coyote (Canis latrans), eastern cottontail (Sylvilagus floridanus), raccoon (Procyon lotor), Virginia opossum (Didelphis virginiana), white-tailed deer (Odocoileus virginianus), woodchuck (Marmota monax), and a Peromyscus sp. This is the first detection of this tick on a rodent host important to the epidemiology of tick-borne pathogens of humans and animals. Finally, we continued to detect the exotic piroplasm parasite, Theileria orientalis Ikeda, in H. longicornis as well as other pathogens, including Rickettsia felis, Anaplasma phagocytophilum (AP-1), and a Hepatozoon sp. previously characterized in Amblyomma americanum. These represent some of the first detections of arthropod-borne pathogens native to the United States in host-seeking H. longicornis. These data increase our understanding of H. longicornis biology in the United States and provide valuable information into the future health risks associated with this tick and pathogens.

ecology↗

bioRxiv2020

LoxTnSeq: Transposon mutagenesis coupled with ultra-sequencing to study large random genome reductions

The Cre-Lox system is a highly versatile and powerful DNA recombinase mechanism, mainly used in genetic engineering to insert or remove desired DNA sequences. It is widely utilised across multiple fields of biology, with applications ranging from plants, to mammals, to microbes. A key feature of this system is its ability to allow recombination between mutant lox sites, traditionally named lox66 and lox71, to create a functionally inactive double mutant lox72 site. However, a large portion of the published literature has incorrectly annotated these mutant lox sites, which in turn can lead to difficulties in replication of methods, design of proper vectors, and confusion over the proper nomenclature. Here, we demonstrate common errors in annotations, the impacts they can have on experimental viability, and a standardised naming convention. We also show an example of how this incorrect annotation can induce toxic effects in bacteria that lack optimal DNA repair systems, exemplified by Mycoplasma pneumoniae. Data SummaryThe authors confirm all supporting data, code and protocols have been provided within the article or through supplementary data files.

synthetic biology↗

bioRxiv2020

Lox'd in translation: Contradictions in the nomenclature surrounding common lox site mutants and their implications in experiments

The removal of unwanted genetic material is a key aspect in many synthetic biology efforts, and often requires preliminary knowledge of which genomic regions are dispensable. Typically, these efforts are guided by transposon mutagenesis studies, coupled to deep-sequencing (TnSeq) to identify insertion points and gene essentiality. However, epistatic interactions can cause unforeseen changes in essentiality after the deletion of a gene, leading to the redundancy of these essentiality maps. Here, we present LoxTnSeq, a new methodology to generate and catalogue libraries of genome reduction mutants. LoxTnSeq combines random integration of lox sites by transposon mutagenesis, and the generation of mutants via cre recombinase, catalogued via deep-sequencing. When LoxTnSeq was applied to the naturally genome reduced bacterium Mycoplasma pneumoniae, we obtained a mutant pool containing 285 unique deletions. These deletions spanned from >50 bp to 28 Kb, which represent 21% of the total genome. LoxTnSeq also highlighted large regions of non-essential genes that could be removed simultaneously, and other non-essential regions that could not, providing a guide for future genome reductions.

bioengineering↗

bioRxiv2020

Comparative Gene Essentiality across the Bacterial Domain

Comparative genomics among bacteria has been used to gain insight into the minimal number of conserved genes in biological pathways. Essentiality studies have provided information regarding which genes are non-dispensable (essential, E) for cell growth. Here, we integrated studies of gene conservation, essentiality and function, performed in 47 diverse bacterial species. We showed there is a modest positive correlation between genome size and number of essential genes. Interestingly, we observed a clear shift in the functions assigned to these essential genes as genome size increases. For instance, essential genes related to transcription and translation dominate small genomes. In contrast, in large genomes functions of essential genes are related with cellular processing and metabolism. Finally, and most intriguing, we found a group of genes that while being highly conserved are also typically non-essential. This suggests that some housekeeping genes confer a significant survival benefit in nature while being non-essential in vitro.

genomics↗

bioRxiv2019

Cannabis, Connectivity, and Coming of Age: Associations between Cannabis Use and Anterior Cingulate Cortex Connectivity during the Transition to Adulthood

BackgroundCannabis use is common among adolescents and emerging adults and is associated with significant adverse consequences for a subset of users. Rates of use peak between the ages of 18-25, yet the neurobiological consequences for neural systems that are actively developing during this time remain poorly understood. In particular, cannabis exposure may interfere with adaptive development of white matter pathways underlying connectivity of the anterior cingulate cortex, including the cingulum and anterior thalamic radiations (ATR).\n\nMethodsThe current study examined the association between cannabis use during adolescence and emerging adulthood and white matter microstructure of the cingulum and ATR among 158 male subjects enrolled in the Pitt Mother & Child Project, a prospective, longitudinal study of risk and resilience among men of low socioeconomic status. Participants were recruited in infancy, completed follow-up assessments throughout childhood and adolescence, and underwent diffusion imaging at age 20 and 22.\n\nResultsAt age 20, moderate cannabis use across adolescence (age 12-19) was associated with higher fractional anisotropy of the cingulum and ATR, relative to both minimal and heavy adolescent use. Longitudinally, moderate and heavy extended cannabis use (age 12-21) was associated with reduced positive change in FA in both pathways from age 20 to 22, relative to minimal use.\n\nConclusionsThese results suggest that precocious white matter development may be linked to increased risk for use, whereas cannabis exposure may delay white matter maturation during the transition to adulthood and potentially impact individuals functioning later in development.

neuroscience↗

bioRxiv2019

Structural models of full-length JAK2 kinase

The protein JAK2 is a prototypical member of the Janus kinase family, and mediates signals from numerous cytokine receptors. The constitutively active V617F mutant of JAK2 is prevalent in many bone marrow disorders, blood cancers, and autoimmune diseases, and is an important drug target. Structures have been determined for each of the four individual domains making up JAK2, and for certain pairs of these domains, but no structure of full-length JAK2 is available, and thus the mechanisms underlying JAK2 regulation and the aberrant activity of the V617F mutant have been incompletely understood. Here we propose structural models of full-length JAK2 in both its active and inactive forms. Construction of these models was informed by long-timescale molecular dynamics simulations. Subsequent mutagenesis experiments showed that mutations at the putative interdomain interfaces modulated JAK2 activity. The models provide a structural basis for understanding JAK2 autoinhibition and activation, and suggest that the constitutive activity of the V617F mutant may arise from a dual effect of destabilizing the inactive conformation and stabilizing the active conformation.

biochemistry↗

bioRxiv2019

Inhibiting fibroblast aggregation in skin wounds unlocks developmental pathway to regeneration

Salamanders are capable of full-thickness skin regeneration where removal of epidermis, dermis and hypodermis results in scar-free repair. What remains unclear is whether regeneration of these tissues recapitulates the cellular events of skin development or occurs through a process unique to regenerative healing. Unfortunately, information on the post-embryonic development of salamander skin is severely lacking, having focused on compartments or cell types, but never on the skin as a complete organ. By examining coordinated development of the epidermis and dermis in axolotls we establish six distinct stages of skin development (I-VI): I-V for normally paedomorphic adults and a sixth stage following metamorphosis. Raising animals either in isolation (zero density pressure) or in groups (density pressure) we find that skin development progresses as a function of animal size and that density directly effects developmental rate. Using keratins, p63, and proliferative markers, we show that although the epidermis lacks visible stratification at early stages of skin development, when the dermis transforms into the stratum spongiosum and stratum compactum keratinocytes differentiate into at least three distinct phenotypes that reveal a cryptic stratification program uncoupled from metamorphosis. Lastly, comparing skin regeneration to skin development, we find that dermal regeneration occurs through a unique process, relying heavily on remodeling of the wound extracellular matrix, rather than proceeding through direct development of a dermal lamella produced by the epidermis. By preventing fibroblast influx into the wound bed using beryllium nitrate, we show that in the absence of fibroblast generated ECM production skin regeneration occurs through an alternate route that recapitulates development.

developmental biology↗