Biology subjects

Hegarty, B. E.

Publications and source records attributed to Hegarty, B. E..

4 recordsLinked to original sources

bioRxiv2023

Natural variation in oxytocin receptor signaling causes widespread changes in brain transcription: a link to the natural killer gene complex

Oxytocin (OXT) is a highly conserved neuropeptide that modulates social cognition, and genetic variation in its receptor gene (Oxtr) is linked to divergent social phenotypes. However, the molecular mechanisms connecting Oxtr genotype to behavioral outcomes remain obscure. Here, we leverage naturally occurring Oxtr polymorphisms in the prairie vole that associate with striatal-specific OXTR density to investigate how OXTR signaling influences brain function. Specifically, we identify OXTR-dependent transcriptomic changes in the natural killer gene complex (NKC) - a genomic region classically associated with peripheral immune function. Centrally, OXTR-regulated NKC genes are positioned to influence microglia-neuron interactions. Consistent with a role for these genes in shaping neuronal connectivity, we show that genetic reduction of OXTR levels leads to increased dendritic spine density on striatal Oxtr-expressing neurons. In addition, we provide support for a similar relation between variation in OXTR mRNA levels and NKC transcription in humans. Together, our findings suggest a role for OXTR signaling in the shaping of neural circuits through transcriptional control of the NKC, outlining a mechanism via which variation in OXTR signaling may influence circuit connectivity to generate diversity in social behaviors.

neuroscience↗

bioRxiv2023

Spatially resolved cell atlas of the teleost telencephalon and deep homology of the vertebrate forebrain

The telencephalon has undergone remarkable diversification and expansion throughout vertebrate evolution, exhibiting striking differences in structural and functional complexity. Nevertheless, fundamental features are shared across vertebrate taxa, such as the presence of distinct regions including the pallium, subpallium, and olfactory structures. Teleost fishes have a uniquely everted telencephalon, which has made it challenging to compare brain regions in fish to those in other vertebrates. Here we combine spatial transcriptomics and single-nucleus RNA-sequencing to generate a spatially-resolved transcriptional atlas of the cichlid fish telencephalon. We then compare cell-types and anatomical regions in the cichlid telencephalon with those in amphibians, reptiles, birds, and mammals. We uncover striking transcriptional similarities between cell populations in the fish telencephalon and subpallial, hippocampal, and cortical cell populations in tetrapods. Ultimately, our work lends new insights into the organization and evolution of conserved cell-types and regions in the vertebrate forebrain.

neuroscience↗

bioRxiv2022

Cellular profiling of a recently-evolved social behavior

Social behaviors are essential for survival and reproduction and vary within and among species. We integrate single nucleus RNA-sequencing (snRNA-seq), comparative genomics, and automated behavior analysis to investigate a recently-evolved social "bower building" behavior in Lake Malawi cichlid fishes. We functionally profile telencephalic nuclei matched to 38 paired behaving/control individuals. Our data suggest bower behavior has evolved in part through divergence in a gene module selectively expressed in a subpopulation of glia lining the pallium. Downregulation of the module is associated with glial departure from quiescence and rebalancing of neuronal subpopulation proportions in the putative homologue of the hippocampus. We show further evidence that behavior-associated excitation of neuronal populations that project to the putative hippocampus mediate glial function and rebalancing. Our work suggests that bower behavior has evolved through changes in glia and region-specific neurogenesis, and more broadly shows how snRNA-seq can generate insight into uncharted behaviors and species.

neuroscience↗

bioRxiv2021

A Snapshot of the Global Drinking Water Virome: Diversity and Metabolic Potential Vary with Residual Disinfectant Use

Viruses are important drivers of microbial community ecology and evolution, influencing microbial mortality, metabolism, and horizontal gene transfer. However, the effects of viruses remain largely unknown in many environments, including in drinking water systems. Drinking water metagenomic studies have offered a whole community perspective of bacterial impacts on water quality, but have not yet considered the influences of viruses. In this study, we address this gap by mining viral DNA sequences from publicly available drinking water metagenomes from distribution systems in six countries around the world. These datasets provide a snapshot of the taxonomic diversity and metabolic potential of the global drinking water virome; and provide an opportunity to investigate the effects of geography, climate, and drinking water treatment practices on viral diversity. Both environmental conditions and differences in sample processing were found to influence the viral composition. Using free chlorine as the residual disinfectant was associated with clear differences in viral taxonomic diversity and metabolic potential, with significantly fewer viral populations and less even viral community structures than observed in distribution systems without residual disinfectant. Additionally, drinking water viruses carry antibiotic resistance genes (ARGs), as well as genes to survive oxidative stress and nitrogen limitation. Through this study, we have demonstrated that viral communities are diverse across drinking water systems and vary with the use of residual disinfectant. Our findings offer directions for future research to develop a more robust understanding of how virus-bacteria interactions in drinking water distribution systems affect water quality.

microbiology↗