Biology subjects

Weir, K.

Publications and source records attributed to Weir, K..

7 recordsLinked to original sources

bioRxiv2025

Heterochronic transcription factor expression drives cone-dominant retina development in 13-lined ground squirrels.

Evolutionary adaptation to diurnal vision in ground squirrels has led to the development of a cone-dominant retina, in stark contrast to the rod-dominant retinas of most mammals. The molecular mechanisms driving this shift remain largely unexplored. Here, we perform single-cell RNA sequencing (scRNA-Seq) and chromatin accessibility profiling (scATAC-Seq) across developmental retinal neurogenesis in the 13-lined ground squirrel (13LGS) to uncover the regulatory basis of this adaptation. We find that 13LGS cone photoreceptors arise not only from early-stage neurogenic progenitors, as seen in rod-dominant species like mice, but also from late-stage neurogenic progenitors. This extended period of cone generation is driven by a heterochronic shift in transcription factor expression, with cone-promoting factors such as Onecut2, Pou2f1, and Zic3 remaining active in late-stage progenitors, and factors that promote cone differentiation such as Thrb, Rxrg, and Mef2c expressed precociously in late-stage neurogenic progenitors. Functional analyses reveal that Zic3 and Mef2c are sufficient to promote cone and repress rod photoreceptor-specific gene expression, and act through species-specific regulatory elements that drive their expression in late-stage progenitors. These results demonstrate that modifications to gene regulatory networks underlie the development of cone-dominant retinas, and provide insight into mechanisms of sensory adaptation and potential strategies for cone photoreceptor regeneration in vision disorders.

neuroscience↗

bioRxiv2023

Identification of conserved gene expression programs activated in multiple modes of torpor across vertebrate clades.

Torpor encompasses adaptations to diverse extreme environmental stressors such as hibernation, aestivation, brumation, and daily torpor. Here we introduce StrokeofGenus, an analytic pipeline that identifies distinct transcriptomic states and conservation of gene expression patterns across studies, tissues, and species. We use StrokeofGenus to study multiple and diverse forms of torpor from publicly available RNA-seq datasets that span eight species and two classes. We identify three transcriptionally distinct states during the cycle of heterothermia: euthermia, torpor, and interbout arousal. We also identify torpor-specific gene expression patterns that are conserved both across tissues and between species with over three hundred million years of evolutionary divergence. We further demonstrate the general conservation of gene expression patterns in multiple forms of torpor, implying a common evolutionary origin for this process. Although here we apply StrokeofGenus to analysis of torpor, it can be used to interrogate any other complex physiological processes defined by transient transcriptomic states. HIGHLIGHTSO_LIStrokeofGenus integrates orthologue annotation, non-negative matrix factorization, and transfer learning for cross-species analysis. C_LIO_LIStrokeofGenus identifies conserved topor-related gene expression patterns across divergent species and cell types. C_LIO_LIHeterothermia has three distinct transcriptomic states. C_LIO_LITorpor-specific gene expression patterns are conserved between species and forms of torpor. C_LI

physiology↗

bioRxiv2023

Prevalence of Avian Influenza Virus in Synanthropic Birds Associated with an Outbreak of Highly Pathogenic Strain EA/AM H5N1

The 2022 - 2023 highly pathogenic avian influenza (HPAI) virus outbreak of H5N1 Eurasian lineage goose/Guangdong clade 2.3.4.4b is the largest in North American history and has significantly impacted wild bird populations and domestic poultry across the United States. Synanthropic birds may play an important role in transmitting the virus laterally to other wild bird species and domestic poultry. Understanding the prevalence of HPAI H5N1 in different avian orders may help inform management decisions and potential risk factors for both wild and domestic bird populations. Following the confirmation of infection of HPAI H5N1 in domestic poultry at two commercial premises in IN, USA, we sampled and tested 266 synanthropic avian species within the Columbiformes and Passeriformes orders and found no detection of the virus at either location. Additionally, laboratories within the National Animal Health Laboratory Network were queried for influenza Type A rRT-PCR assay test results from morbidity and mortality events in wild birds, consisting of 10,786 birds tested across eight orders and 1,666 avian influenza virus detections. Query results were assessed by taxonomic groups for viral prevalence and suggested that the virus most often was observed in predatory and scavenging birds. Although detections were found in non-predatory synanthropic birds including the orders Columbiformes, Galliformes, and Passeriformes, the risk of transmission from and between these groups appears comparatively low, with apparent prevalence rates of 0.0090, 0.0688, and 0.0147, respectively. The highest prevalence was observed in raptors (0.2514), with prevalence rates in exclusively scavenging Cathartidae reaching up to 0.5333. There is strong evidence that consumption of infected tissues is a key pathway for transmission of avian influenza viruses. Understanding the impact of the 2022 - 2023 HPAI outbreak in wild bird populations can provide pertinent information on viral transmission, disease ecology, and risk to humans and agriculture.

ecology↗

bioRxiv2023

Molecular tuning of sea anemone stinging

Jellyfish and sea anemones fire single-use, venom-covered barbs to immobilize prey or predators. We previously showed that the anemone Nematostella vectensis uses a specialized voltage-gated calcium (CaV) channel to trigger stinging in response to synergistic prey-derived chemicals and touch (Weir et al., 2020). Here we use experiments and theory to find that stinging behavior is suited to distinct ecological niches. We find that the burrowing anemone Nematostella uses uniquely strong CaV inactivation for precise control of predatory stinging. In contrast, the related anemone Exaiptasia diaphana inhabits exposed environments to support photosynthetic endosymbionts. Consistent with its niche, Exaiptasia indiscriminately stings for defense and expresses a CaV splice variant that confers weak inactivation. Chimeric analyses reveal that CaV{beta} subunit adaptations regulate inactivation, suggesting an evolutionary tuning mechanism for stinging behavior. These findings demonstrate how functional specialization of ion channel structure contributes to distinct organismal behavior.

physiology↗

bioRxiv2021

Gene regulatory networks controlling temporal patterning, neurogenesis and cell fate specification in the mammalian retina.

Gene regulatory networks (GRNs), consisting of transcription factors and their target cis- regulatory sequences, control neurogenesis and cell fate specification in the developing central nervous system, but their organization is poorly characterized. In this study, we performed integrated single-cell RNA- and scATAC-seq analysis in both mouse and human retina to profile dynamic changes in gene expression, chromatin accessibility and transcription factor footprinting during retinal neurogenesis. We identified multiple interconnected, evolutionarily-conserved GRNs consisting of cell type-specific transcription factors that both activate expression of genes within their own network and often inhibit expression of genes in other networks. These GRNs control state transitions within primary retinal progenitors that underlie temporal patterning, regulate the transition from primary to neurogenic progenitors, and drive specification of each major retinal cell type. We confirmed the prediction of this analysis that the NFI transcription factors Nfia, Nfib, and Nfix selectively activate expression of genes that promote late-stage temporal identity in primary retinal progenitors. We also used GRNs to identify additional transcription factors that promote (Insm1/2) and inhibit (Tbx3, Tcf7l1/2) rod photoreceptor specification in postnatal retina. This study provides an inventory of cis- and trans-acting factors that control retinal development, identifies transcription factors that control the temporal identity of retinal progenitors and cell fate specification, and will potentially guide cell-based therapies aimed at replacing retinal neurons lost due to disease.

neuroscience↗

bioRxiv2020

Regulation of retinal neurogenesis by somatostatin signaling.

Neuropeptides have been reported to regulate progenitor proliferation and neurogenesis in the central nervous system. However, these studies have typically been conducted using pharmacological agents in ex vivo preparations, and in vivo evidence for their developmental function is generally lacking. Recent scRNA-Seq studies have identified multiple neuropeptides and their receptors as being selectively expressed in neurogenic progenitors of the embryonic mouse and human retina. This includes Sstr2, whose ligand somatostatin is transiently expressed by immature retinal ganglion cells. By analyzing retinal explants treated with selective ligands that target these receptors, we found that Sstr2-dependent somatostatin signaling induces a dose-dependent inhibition of photoreceptor generation while increasing the relative fraction of primary progenitor cells. These effects were confirmed by scRNA-Seq analysis of retinal explants and abolished in Sstr2-deficient retinas. Although no changes in the relative fraction of primary progenitors or photoreceptor precursors were observed in Sstr2-deficient retinas in vivo, scRNA-Seq analysis demonstrated accelerated differentiation of neurogenic progenitors. We conclude that Sstr2 signaling may act to negatively regulate retinal neurogenesis in combination with other retinal ganglion cell-derived secreted factors such as Shh, although in vivo Sstr2 is dispensable for normal retinal development.

neuroscience↗

bioRxiv2020

A molecular filter for the cnidarian stinging response

All animals detect and integrate diverse environmental signals to mediate behavior. Cnidarians, including jellyfish and sea anemones, both detect and capture prey using stinging cells called nematocytes which fire a venom-covered barb via an unknown triggering mechanism. Here, we show that nematocytes from Nematostella vectensis use a specialized voltage-gated calcium channel (nCav) to distinguish salient sensory cues and control the explosive discharge response. Adaptations in nCav confer unusually-sensitive, voltage-dependent inactivation to inhibit responses to non-prey signals, such as mechanical water turbulence. Prey-derived chemosensory signals are synaptically transmitted to acutely relieve nCav inactivation, enabling mechanosensitive-triggered predatory attack. These findings reveal a molecular basis for the cnidarian stinging response and highlight general principles by which single proteins integrate diverse signals to elicit discrete animal behaviors.

physiology↗