Biology subjects

Wilkinson, G.

Publications and source records attributed to Wilkinson, G..

3 recordsLinked to original sources

bioRxiv2026

Common and Sex-Biased Muscle Transcriptomic Aging Signatures Across Diverse Species

Sex differences in lifespan are widespread yet inconsistent across the animal kingdom. In mammals, XX females outlive XY males in over 60% of species, while this pattern reverses in birds, where ZZ males have a higher life expectancy. These sex differences raise the question of whether sex-biased aging biomarkers (age-associated molecular signatures that reflect biological aging processes) can be identified based on transcriptomic data and whether such markers are shared across taxa. To identify sex-biased aging biomarkers, we analyzed sex-specific skeletal muscle transcriptomes (RNA-seq) from young and old individuals of six species spanning major evolutionary lineages. Four female-biased and 18 male-biased aging biomarkers were identified across all species. Three shared aging biomarkers were also identified in both sexes of all species: Na Channel, Heat Shock Protein 70 (HSP70), and Secreted Protein Acidic and Rich in Cysteine (SPARC). Particularly, age-associated changes in the HSP70 family are suggestive of a shared decline in proteostasis, a hallmark of aging observed across both model and non-model organisms. Furthermore, using an Ornstein-Uhlenbeck (OU) model applied to orthogroup phylogenies, we identified lineage- and sex-dependent expression shifts in shared aging biomarkers. In addition, sex-biased orthogroups revealed age-associated alterations in muscle structure and function in females, whereas mitochondrial and metabolic pathways were predominantly changed in males, indicating divergent mechanisms in muscle aging between sexes. Together, these findings identified a set of transcriptional aging signatures, both shared and sex-biased, that are detectable across diverse evolutionary lineages, providing insight into shared and divergent molecular mechanisms underlying aging.

genomics↗

bioRxiv2025

Gain and loss of function changes in CACNA1C affect neuronal networks through divergent pathways

BackgroundCACNA1C encodes the pore-forming subunit of the L-type calcium channel Cav1.2. Common variants in CACNA1C are associated with psychiatric disorders, while rare single-nucleotide variants cause CACNA1C-related disorder (CRD), a multi-system disorder with symptoms that include autism spectrum disorder (ASD), intellectual disability and seizures. However, the cellular mechanisms linking CACNA1C dysfunction to neurodevelopmental phenotypes remain poorly understood. MethodsWe generated isogenic CACNA1C loss-of-function (LoF) induced pluripotent stem cell (iPSC) lines and reprogrammed a line from an individual carrying a novel gain-of-function (GoF) variant in CACNA1C. Neuronal activity was assessed using multi-electrode arrays (MEA), pharmacological manipulation, and gene expression analysis. Early developmental phenotypes were examined using qRT-PCR, immunocytochemistry, and RNA sequencing. ResultsLoF and GoF patient-derived neurons displayed opposing alterations in network dynamics. Pharmacological and molecular assays indicated that these network differences were associated with dysregulated GABAergic signalling. Early developmental analysis revealed that loss of CACNA1C altered rosette morphology, CREB phosphorylation, and transcriptional programs related to axonogenesis and synaptic signalling, indicating effects on neuronal differentiation. The patient line exhibited opposing phenotypes, reflecting variant-specific effects. ConclusionsThese findings demonstrate that Cav1.2 regulates excitatory-inhibitory balance, network organization, and aspects of neurodevelopment. Divergent effects of LoF and GoF variants highlight how altered Cav1.2 signalling contributes to variable neurodevelopmental phenotypes, including ASD and epilepsy, and establish a framework for defining CACNA1C variant effects in human neurons.

neuroscience↗

bioRxiv2019

Behaviour, biology, and evolution of vocal learning in bats

The comparative approach can provide insight into the evolution of human speech, language, and social communication by studying relevant traits in animal systems. Bats are emerging as a model system with great potential to shed light on these processes given their learned vocalisations, close social interactions, and mammalian brains and physiology. A recent framework outlined the multiple levels of investigation needed to understand vocal learning across a broad range of non-human species including cetaceans, pinnipeds, elephants, birds and bats. Herein we apply this framework to the current state of the art in bat research. This encompasses our understanding of the abilities bats have displayed for vocal learning, what is known about the timing and social structure needed for such learning, and current knowledge about the prevalence of the trait across the order. It also addresses the biology (vocal tract morphology, neurobiology, and genetics) and phylogenetics of this trait. We conclude by highlighting some key questions that should be answered to advance our understanding of the biological encoding and evolution of speech and spoken communication.

animal behavior and cognition↗