Biology subjects

George, J. M.

Publications and source records attributed to George, J. M..

5 recordsLinked to original sources

bioRxiv2026

Multiome Profiling Reveals Astrocyte and Neuroendocrine Targets of Prenatal Acoustic Programming in Zebra Finch Embryos

Climate change is driving more frequent and severe heat events, yet the developmental mechanisms by which organisms anticipate and adapt to thermal stress remain poorly understood. In zebra finches (Taeniopygia guttata), parents exposed to extreme heat emit distinctive "heat call" vocalizations during late incubation that trigger adaptive phenotypic responses in offspring, including altered growth, thermoregulation, and reproductive success. Recent transcriptomic analysis revealed that prenatal heat call exposure induces hypothalamic gene expression changes enriched in non-neuronal populations, but cellular heterogeneity has obscured which cell types are primary targets and the regulatory mechanisms underlying acoustic programming. Here, we performed single-nucleus multiome sequencing to generate a cell-type-resolved atlas of gene expression and chromatin accessibility in the late-stage embryonic zebra finch hypothalamus. We find that heat call exposure selectively remodels astrocyte regulatory landscapes, with most playback-responsive chromatin changes localized to glial populations like astrocytes, challenging neuron-centric models of developmental programming. Motif enrichment and gene regulatory network analysis showed Nuclear Factor I-C, AP-1, and Notch pathway components - canonical drivers of the gliogenic switch - coordinate this response. Chromatin co-accessibility analysis revealed extensive astrocyte-specific enhancer-promoter rewiring at developmental signaling hubs, and pseudotemporal analysis identified condition-associated shifts in developmental trajectories and astrocyte gene-expression dynamics consistent with altered gliogenic programs. In parallel, we identified sex-dimorphic regulation of transthyretin in glutamatergic neurons of the paraventricular nucleus, linking acoustic programming to thyroid-dependent neuroendocrine pathways. These findings suggest that prenatal acoustic experience engages astrocyte-selective epigenetic priming and neuroendocrine transcriptional responses that may reshape hypothalamic developmental programs under predicted thermal environments.

developmental biology↗

bioRxiv2026

Programming of Embryonic Blood Brain Barrier and Neurovascular Transcriptome by an Anticipatory Acoustic Signal of Heat in the Zebra Finch

AbstractOrganisms have evolved mechanisms to adjust to rapid environmental change. A dramatic example is the Australian zebra finch, where incubating parents produce an acoustic signal ("heat call") during extreme heat, triggering adaptive phenotypic plasticity in their offspring growth, thermoregulation, and reproductive success. To elucidate for the first time the molecular mechanisms underlying heat call-induced programming, we hypothesized a prenatal shift in hypothalamic gene expression, given the hypothalamuss central role in neuroendocrine signaling controlling metabolism and growth. In addition, we tested whether prenatal heat-call exposure induces local changes in the brain, to protect this highly heat-sensitive organ from upcoming heat challenges. We exposed zebra finch embryos to chronic playback of parental heat calls or control calls, then isolated the hypothalamus for RNA sequencing to identify differentially expressed genes and gene regulatory networks. Heat-call exposure elicited modest neuroendocrine gene expression changes, but robust downregulation of genes tied to muscle contraction and cytoskeletal dynamics, with evidence of isoform usage shifts. These changes were prominently localized to hypothalamic neurovascular endothelial, mural, and ependymal cell populations, forming the blood-brain barrier (BBB). Because embryos experienced heat-associated sound, but not heat itself, and changes matched the loosening of the BBB to avoid breakages, these transcriptomic shifts likely represent an anticipatory response to enhance subsequent brain resilience to heat. Our study provides the first genome-wide characterization of embryonic hypothalamic gene expression in a songbird and reveals that prenatal acoustic cues can developmentally program neurovascular systems, expanding current understanding of developmental plasticity under climate change.

developmental biology↗

bioRxiv2025

A Quantitative Polymerase Chain Reaction Protocol for Sex Identification of Zebra Finch and Chicken Using Blood Samples

Studies of early development in birds typically rely on PCR analysis of genomic DNA to identify embryonic or neonatal sex. In zebra finches and other birds, males are the homogametic sex (ZZ) while females are heterogametic (ZW), and females are distinguished by the presence of specific sequences on the female-specific W chromosome. However, when only a single W locus is analyzed, lack of a PCR product in a sample could potentially arise from genetic variation or technical failure of the amplification, leading to false identification of female samples as males. To mitigate this concern, we developed an approach that targets two different W loci, using SYBR-based quantitative PCR to analyze amplification curves. We applied this method to determine sex of 30 zebra finch embryos (embryonic day 13) and subsequently confirmed genetic sex by brain transcriptome sequencing. We also identified and tested primer sets that are effective for sex determination in chickens.

developmental biology↗

bioRxiv2020

Intestinal inflammation and altered gut microbiota associated with inflammatory bowel disease renders mice susceptible to Clostridioides difficile colonization and infection

Clostridioides difficile has emerged as a noteworthy pathogen in patients with inflammatory bowel disease (IBD). Concurrent IBD and CDI is associated with increased morbidity and mortality compared to CDI alone. IBD is associated with alterations of the gut microbiota, an important mediator of colonization resistance to C. difficile. Here, we describe and utilize a mouse model to explore the role of intestinal inflammation in susceptibility to C. difficile colonization and subsequent disease severity in animals with underlying IBD. Helicobacter hepaticus, a normal member of the mouse gut microbiota, was used to trigger inflammation in the distal intestine akin to human IBD in mice that lack intact IL-10 signaling. Development of IBD resulted in a distinct intestinal microbiota community compared to non-IBD controls. We demonstrate that in this murine model, IBD was sufficient to render mice susceptible to C. difficile colonization. Mice with IBD were persistently colonized by C. difficile, while genetically identical non-IBD controls were resistant to C. difficile colonization. Concomitant IBD and CDI was associated with significantly worse disease than unaccompanied IBD. IL-10-deficient mice maintained gut microbial diversity and colonization resistance to C. difficile in experiments utilizing an isogenic mutant of H. hepaticus that does not trigger intestinal inflammation. These studies in mice demonstrate that the IBD-induced microbiota is sufficient for C. difficile colonization and that this mouse model requires intestinal inflammation for inducing susceptibility to CDI in the absence of other perturbations, such as antibiotic treatment. IMPORTANCEThe incidence of CDI continues to increase significantly among patients with IBD, independent of antibiotic use, yet the relationship between IBD and increased risk for CDI remains to be understood. However, antibiotic-induced perturbations of the gut microbiota may mask mechanisms specific to IBD-induced C. difficile susceptibility and infection. Our study sought to describe and utilize a mouse model to specifically explore the relationship between the IBD-induced gut microbial community and susceptibility to C. difficile colonization and CDI development. We demonstrate that IBD is sufficient for C. difficile colonization and infection in mice and results in significantly worse disease than IBD alone, representing a murine model that recapitulates human IBD and CDI comorbidity. Furthermore, this model requires IBD-induced inflammation to sculpt a microbiota permissible to C. difficile colonization. Use of this model will aid in developing new clinical approaches to predict, diagnose, and treat C. difficile infection in the IBD population.

microbiology↗

bioRxiv2020

Towards complete and error-free genome assemblies of all vertebrate species

High-quality and complete reference genome assemblies are fundamental for the application of genomics to biology, disease, and biodiversity conservation. However, such assemblies are only available for a few non-microbial species1-4. To address this issue, the international Genome 10K (G10K) consortium5,6 has worked over a five-year period to evaluate and develop cost-effective methods for assembling the most accurate and complete reference genomes to date. Here we summarize these developments, introduce a set of quality standards, and present lessons learned from sequencing and assembling 16 species representing major vertebrate lineages (mammals, birds, reptiles, amphibians, teleost fishes and cartilaginous fishes). We confirm that long-read sequencing technologies are essential for maximizing genome quality and that unresolved complex repeats and haplotype heterozygosity are major sources of error in assemblies. Our new assemblies identify and correct substantial errors in some of the best historical reference genomes. Adopting these lessons, we have embarked on the Vertebrate Genomes Project (VGP), an effort to generate high-quality, complete reference genomes for all ~70,000 extant vertebrate species and help enable a new era of discovery across the life sciences.

genomics↗