Biology subjects

Glasgow, E.

Publications and source records attributed to Glasgow, E..

13 recordsLinked to original sources

bioRxiv2026

The genetic basis of extra-lobed leaves in ivyleaf morning glory (Ipomoea hederacea)

Intraspecific leaf shape variation is common among angiosperms. Ivyleaf morning glory (Ipomoea hederacea) has become a useful system for studying the genetics and ecology of leaf shape variation as this species exhibits two leaf shapes: leaves with entire margins, and 3-lobed leaves. It is known that these phenotypes are controlled by a single locus, and differ in their ecophysiology, geographic distribution, ecology, and fitness. However, individuals producing leaves with 1-2 extra lobes have also been observed, but the genetic basis of these phenotypes have not been described. To investigate the genetic basis of extra-lobing, we compared phenotypic distributions of leaf shapes of an F2 generation to Mendelian ratios for a single locus trait, and conducted a bulked segregant analysis to uncover quantitative trait loci. Our results suggest that producing extra-lobed leaves has a complex genetic basis and that there are multiple QTLs underlying this phenotype containing potential candidate genes involved with auxin distribution and leaf development. Whether these extra-lobed phenotypes also differ in terms of their physiology and ecology remains unexplored.

plant biology↗

bioRxiv2026

A rare deletion of BZ1 in the ivy-leaf morning glory eliminates anthocyanin-based pigmentation.

Anthocyanin biosynthesis is a highly branched network with upstream mutations leading to the loss of many other branches beyond just anthocyanins like flavonols, isoflavonoids, and proanthocyanidins. Consequently, disentangling the specific effects of anthocyanins on plant fitness from those of other branches is difficult unless a mutant impacting the terminal step of anthocyanin biosynthesis can be found. We discovered an Ipomoea hederacea plant (ivy-leaf morning glory) lacking anthocyanins due to a genetic deletion in the terminal step of the anthocyanin biosynthetic pathway. Anthocyanin loss follows a recessive, Mendelian inheritance pattern. Anthocyanin loss is perfectly correlated with a lack of expression of the anthocyanin biosynthesis gene IhUF3GT1 (anthocyanidin-3-O-glucosyltransferase). IhUF3GT1 is the gene most strongly and consistently differentially expressed between unpigmented and pigmented flowers in F2 siblings. A deletion of half of the IhUF3GT1 gene which includes the start codon is the genetic basis underlying a loss of IhUF3GT1 expression and, consequently, anthocyanins in unpigmented plants. The IhUF3GT1 deletion is rare and unique to the unpigmented line. Genome coverage analyses demonstrate that no other pigmented I. hederacea line (of 123 screened) has a loss-of-function mutation in IhUF3GT1. Furthermore, we confirm cosegregation of the IhUF3GT1 deletion with the unpigmented phenotype in F3 progeny from a cross where all unpigmented plants are homozygous for the IhUF3GT1 deletion. Taken together, we describe the genetic basis of a novel unpigmented mutant in I. hederacea, creating a potentially important model for studying the fitness effects of anthocyanin loss.

evolutionary biology↗

bioRxiv2026

Newly arisen indel governs a leaf shape polymorphism in the Ivy Leaf Morning Glory (Ipomoea hederacea)

Leaf shape varies widely across plant taxa and has repeatedly been shown to affect ecophysiology, interspecific interactions, and fitness. We used population genomics, genome wide association studies (GWAS), and comparative genomics to determine the genetic basis and evolutionary history of an uncharacterized Mendelian leaf shape polymorphism in Ipomoea hederacea. To do so, we assembled a reference genome and generated whole genome sequencing for 123 individuals from 55 populations. We identified a 117 kb indel that perfectly co-segregates with leaf shape by conducting a GWAS and assessing differences in coverage. Syntenic orthologs for genes on the indel were present in five other Ipomoea species with various leaf shapes, indicating the indel is a newly arisen deletion in I. hederacea despite similar leaf shape phenotypes in the other species. More broadly, these results illustrate how a range of leaf shape phenotypes can be produced by distinct genetic mechanisms even in closely related species. Although none of the genes on the indel itself are known leaf shape candidates, there are multiple leaf shape candidate genes in close proximity that are involved in the auxin biosynthesis pathway. Additionally, the genes within the indel have gene functions that could affect other potentially ecologically relevant traits that have previously been shown to be associated with leaf shape in I. hederacea. Therefore, the pleiotropic effects of the indel polymorphism can have important implications for understanding the ecological mechanisms influencing a well-documented leaf shape latitudinal cline in I. hederacea. Significance StatementIpomoea hederacea has been used to investigate the ecological and evolutionary effects of leaf shape because of a well-documented latitudinal leaf shape cline governed by an uncharacterized Mendelian polymorphism in this species. We identified a 117 kb indel that perfectly co-segregates with leaf shape in I. hederacea. The indel appears to be a distinct genetic mechanism than those governing similar leaf shapes in other closely related Ipomoea species. Additionally, possible pleiotropic effects of the indel on other traits has important implications for understanding the ecology and evolution of leaf shape variation in I. hederacea. Therefore, the results and the new genomic resources that we developed will facilitate future work understanding the genetic, developmental, and ecological mechanisms governing leaf shape variation.

plant biology↗

bioRxiv2025

Simulated drought with Polyethylene-Glycol (PEG) decreases above-ground performance and increases nodulation in the legume Medicago lupulina

Under climate change, understanding how plants and crops respond to drought is essential for basic research in ecology and evolution, and improving agricultural resilience. One common method of simulating drought in experimental conditions is by applying polyethylene glycol (PEG) to plants. We investigated drought growth responses in Medicago lupulina (black medic) using PEG to simulate drought stress. We grew Medicago lupulina plants inoculated with Sinorhizobium meliloti in Magenta boxes under controlled conditions and randomly assigned them to one of three treatments: a control, PEG applied to the bottom (PEG added to the bottom-watering container of a magenta box), or PEG applied from the top (PEG poured over the growth media). After 60 days, we measured true leaf number, nodule count, and below- and above-ground dry biomass. PEG treatments significantly reduced above-ground growth, including total biomass and leaf number, but unexpectedly increased nodulation. Our results suggest that while PEG effectively simulates drought stress on above-ground growth parameters, it may not accurately simulate drought effects on rhizobial symbiosis. PEG treatments had no effect on below-ground biomass, suggesting that increased nodulation is not a result of increased plant investment in below-ground growth under simulated drought. We hypothesize that PEG, as a persistent liquid that plants do not absorb, created conditions favorable for nodulation. Overall, these results highlight the importance of interpreting PEG-simulated drought experiments with caution when assessing mutualistic interactions.

plant biology↗

bioRxiv2025

Rapid evolution of synteny associated with multiple origins of dioecy and XY sex determination

Chromosomal rearrangements are a major driver of evolutionary innovation, shaping processes including local adaptation, speciation, and sex chromosome evolution. Multispecies synteny datasets are rich in information on the drivers of genomic rearrangement, but statistical approaches that enable insights to be obtained from this information are still in their infancy. Here, we present a novel framework for the application of phylogenetic comparative methods to multispecies synteny datasets. We apply this approach to Rumex, a clade of flowering plants that exhibits rapid karyotypic evolution, including multiple origins of XY sex determination from hermaphroditic ancestors. Leveraging new genome assemblies, we find evidence for accelerated syntenic evolution associated with evolutionary transitions to dioecy, highlighting how explicit phylogenetic hypothesis testing can generate new insights into adaptive hypotheses for rearrangements.

evolutionary biology↗

bioRxiv2025

The ecological dynamics and consequences of phytoplasma in a spring ephemeral

Ecologists have long sought to link within-population dynamics to patterns of species occurrence and persistence across the range. Theoretical models suggest pathogens have important implications for plant populations and perhaps even limit plant distributions, though more empirical evidence is needed, especially in wild plant populations. In the field, we characterized the infection dynamics of phytoplasma, a vectored and sterilizing bacterial pathogen, in wild populations of white trillium. We identified the highest molecular matches for the local bacterial strain and putative vectors. We then leveraged iNaturalist data to reveal patterns and potential drivers of phytoplasma occurrence across the range of white trillium. Within populations, we found that phytoplasma symptoms were more likely in low host density plots, where insects occupied a higher proportion of trillium, indicative of an encounter-dilution effect. Leafhoppers in the genus Empoasca were positive for phytoplasma, suggesting they are a candidate vector of disease between trilliums at our field site. The closest match to our local phytoplasma was related to Candidatus Phytoplasma pruni, ribosomal group 16SrIII-F. Phytoplasma symptoms were widely distributed across trilliums range, even at range edges, and probability of symptoms was significantly increased by proximity to cropland. We studied the impacts of a sterilizing, vector-transmitted pathogen on host plant populations and patterns of infection across host range. Our results suggest sap-feeding insects do not occupy all hosts at high host densities, thereby reducing transmission and leading to higher likelihood of finding infection at low host densities, and a higher proportion of host plants infected at low host densities. At a range-wide scale, we found evidence that the pathogen was able to persist across both the core and edge of host ranges. Thus, negative-density dependent sterilizing pathogens may challenge host populations across the range.

ecology↗

bioRxiv2025

MMP-2/9 inhibition modulates sharp wave abundance, inhibitory proteoglycan sulfation, and fear memory in juvenile zebrafish: relevance to affective disorders

Sharp wave ripple (SWR) events, present in diverse species, spontaneously occur in the hippocampus during quiescent restfulness and slow-wave sleep. SWRs comprise a negative deflection, the sharp wave (SW) event with an often-superimposed ripple (R) and are the neural correlates of memory consolidation and recall. The Anterodorsolateral lobe (ADL) (zebrafish hippocampal homologue) exhibits SW and SWR events, and since SWs initiate SWRs, their abundance typically shows the same directionality. In previous work, we observed matrix metalloproteinase-9 (MMP-9)-dependent effects on depression-relevant behaviors, perineuronal net (PNN) levels, and SWR abundance in the adult rodent hippocampus. Here, we investigate MMP-2/9-dependent effects on biochemical, behavioral, and neurophysiological endpoints in juvenile zebrafish and zebrafish at the transition from the late juvenile period to early adulthood. With MMP-2/9 inhibition, juvenile zebrafish showed reduced SW amplitude and abundance together with increased fear memory retention and reduced sociability. Juvenile zebrafish also showed an increased percentage of longer-duration SW events. Except for a reduction in SW amplitude, these changes were not observed at the transition from late juvenile to early adulthood. These changes were accompanied by increased levels of chondroitin sulfate (CS) proteoglycan 4-O-sulfation, which modulates PNNs and excitatory-to-inhibitory (E/I) balance. Discontinuation of MMP-2/9 inhibition in juvenile zebrafish normalized deficits in ADL SW abundance and sociability. Together, these findings show that MMP-2/9 significantly influences E/I balance and learning and memory during the highly plastic juvenile period in zebrafish. Findings also have relevance to an emerging appreciation of PNN changes that may contribute to altered neuronal oscillations and mood or cognition.

neuroscience↗

bioRxiv2024

Pose analysis in free-swimming adult zebrafish, Danio rerio:"fishy" origins of movement design

Movement requires maneuvers that generate thrust to either make turns or move the body forward in physical space. The computational space for perpetually controlling the relative position of every point on the body surface can be vast. We hypothesize the evolution of efficient design for movement that minimizes active (neural) control by leveraging the passive (reactive) forces between the body and the surrounding medium at play. To test our hypothesis, we investigate the presence of stereotypical postures during free-swimming in adult zebrafish, Danio rerio. We perform markerless tracking using DeepLabCut, a deep learning pose estimation toolkit, to track geometric relationships between body parts. To identify putative clusters of postural configurations obtained from twelve freely behaving zebrafish, we use unsupervised multivariate time-series analysis (B-SOiD machine learning software). When applied to single individuals, this method reveals a best-fit for 36 to 50 clusters in contrast 86 clusters for data pooled from all 12 animals. The centroids of each cluster obtained over 14,000 sequential frames recorded for a single fish represent an apriori classification into relatively stable "target body postures" and inter-pose "transitional postures" that lead to and away from a target pose. We use multidimensional scaling of mean parameter values for each cluster to map cluster-centroids within two dimensions of postural space. From a post-priori visual analysis, we condense neighboring postural variants into 15 superclusters or core body configurations. We develop a nomenclature specifying the anteroposterior level/s (upper, mid and lower) and degree of bending. Our results suggest that constraining bends to mainly three levels in adult zebrafish preempts the neck, fore- and hindlimb design for maneuverability in land vertebrates.

animal behavior and cognition↗

bioRxiv2023

Loss of the mitochondrial citrate carrier, SLC25A1/CIC disrupts embryogenesis via 2-Hydroxyglutarate

Germline inactivating mutations of the SLC25A1 gene contribute to various human developmental disorders, including combined D/L-2-hydroxyglutaric aciduria (D/L-2HGA), a severe systemic syndrome characterized by the accumulation of both enantiomers of 2-hydroxyglutaric acid (2HG). The mechanisms by which SLC25A1 deficiency leads to this disease and the role of 2HG are unclear and no therapies exist. We now show that mice lacking both Slc25a1 alleles display a spectrum of alterations that resemble human D/L-2HGA. Mechanistically, SLC25A1 loss results in a proliferation defect and activates two distinct senescence pathways, oncogene-induced senescence (OIS) and mitochondrial dysfunction-induced senescence (MiDAS), both involving the p53 tumor suppressor and driven by two discernible signals: the accumulation of 2HG, inducing OIS, and mitochondrial dysfunction, triggering MiDAS. Inhibiting these senescence programs or blocking p53 activity reverses the growth defect caused by SLC25A1 dysfunction and restores proliferation. These findings reveal novel pathogenic roles of senescence in human disorders and suggest potential strategies to correct the molecular alterations caused by SLC25A1 loss.

developmental biology↗

bioRxiv2023

Sharp wave ripple coupling in zebrafish hippocampus and basolateral amygdala

The mammalian hippocampus exhibits sharp wave events (1-30 Hz) with an often-present superimposed fast ripple oscillation (120-200 Hz) forming a sharp wave ripple (SWR) complex. During slow wave sleep or consummatory behaviors, SWRs result from the sequential spiking of hippocampal cell assemblies initially activated during imagined or learned experiences. SWRs occur in tandem with cortical/subcortical assemblies critical to the long-term storage of specific memory types. Leveraging juvenile zebrafish, we show that SWR events in their hippocampal homologue, the anterodorsolateral lobe (ADL), in ex vivo whole-brains are locally generated and maintained. SWR events were also recorded in the basolateral amygdala (BLA). Concomitant single cell calcium imaging and local field potential (LFP) recordings showed that BLA SWs couple to ADL SWs. Calcium imaging recordings of whole-brains demonstrated that ADL and BLA SWRs are endogenously and spontaneously silenced by the activation of a more caudal population of putative cholinergic cells. Electrical stimulation of this caudal region silenced ADL SWs. Our results suggest that the SWR-generating circuit is evolutionarily conserved through shared acetylcholine modulating mechanisms. These findings further our understanding of neuronal population dynamics in the zebrafish brain and highlights their advantage for simultaneously recording SW/SWRs and single cell activity in diverse brain regions.

neuroscience↗

bioRxiv2021

Zebrafish xenografts to isolate unique human breast cancer metastatic cell populations

Cancer metastasis is a critical culprit frequently blamed for treatment failure, drug resistance, poor prognosis, and high mortality rate among all human cancers. Laboratory efforts to isolate metastatic cell populations have typically been confined to mouse models, which are time-consuming and expensive. Here, we present a model system based on xenografting zebrafish embryos to select for cells that are predisposed to progress through the early stages of metastasis. This model requires only 3-5 days to achieve distinct intravasation to the zebrafish circulatory system. The metastatic cells are easily tracked in real-time as they migrate, as well as isolated and propagated in vitro. Once expanded, molecular characterization of the serially derived invasive cell populations from the tails of the zebrafish accurately predicts genes, signaling pathways, protein-protein interactions, and differential splicing products that are important for an invasive phenotype. This zebrafish model therefore offers a high-throughput and robust method for identifying gene targets critical for cancer metastasis.

cancer biology↗

bioRxiv2021

Fibroblast activation protein regulates natural killer cell migration, extravasation and tumor infiltration

Natural killer (NK) cells play a critical role in physiologic and pathologic conditions such as pregnancy, infection, autoimmune disease and cancer. In cancer, numerous strategies have been designed to exploit the cytolytic properties of NK cells, with variable success. A major hurdle to NK-cell focused therapies is NK cell recruitment and infiltration into tumors. While the chemotaxis pathways regulating NK recruitment to different tissues are well delineated, the mechanisms human NK cells employ to physically migrate are ill-defined. We show for the first time that human NK cells express fibroblast activation protein (FAP), a cell surface protease previously thought to be primarily expressed by activated fibroblasts. FAP degrades the extracellular matrix to facilitate cell migration and tissue remodeling. We used novel in vivo zebrafish and in vitro 3D culture models to demonstrate that FAP knock out and pharmacologic inhibition restrict NK cell migration, extravasation, and invasion through tissue matrix. Notably, forced overexpression of FAP promotes NK cell invasion through matrix in both transwell and tumor spheroid assays, ultimately increasing tumor cell lysis. Additionally, FAP overexpression enhances NK cells invasion into a human tumor in immunodeficient mice. These findings demonstrate the necessity of FAP in NK cell migration and present a new approach to modulate NK cell trafficking and enhance cell-based therapy in solid tumors. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=129 SRC="FIGDIR/small/429622v3_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@d6d9e5org.highwire.dtl.DTLVardef@17b6790org.highwire.dtl.DTLVardef@cc581eorg.highwire.dtl.DTLVardef@1ad2129_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2019

Estrogen-related receptor beta activation and isoform shifting by cdc2-like kinase inhibition restricts migration and intracranial tumor growth in glioblastoma

Glioblastoma (GBM; grade 4 glioma) is a highly aggressive and incurable tumor. GBM has recently been characterized as highly dependent on alternative splicing, a critical driver of tumor heterogeneity and plasticity. Estrogen-related receptor beta (ERR{beta}, ESRRB, NR3B2) is an orphan nuclear receptor expressed in the brain, where alternative splicing of the 3 end of the pre-mRNA leads to the production of three validated ERR{beta} protein products - ERR{beta} short form (ERR{beta}sf), ERR{beta}2, and ERR{beta} exon 10-deleted (ERR{beta}-{Delta}10). Our prior studies have shown the ERR{beta}2 isoform to play a role in G2/M cell cycle arrest and induction of apoptosis, in contrast to the function of the shorter ERR{beta}sf isoform in senescence and G1 cell cycle arrest. In this study, we sought to better define the role of the pro-apoptotic ERR{beta}2 isoform in GBM. We show that the ERR{beta}2 isoform is located in the nucleus, but also the cytoplasm. ERR{beta}2 suppresses GBM cell migration, interacts with the actin nucleation-promoting factor cortactin, and an ERR{beta} agonist is able to remodel the actin cytoskeleton and similarly suppress GBM cell migration. We further show that inhibition of the splicing regulatory cdc2-like kinases (CLKs) in combination with an ERR{beta} agonist shifts isoform expression in favor of ERR{beta}2 and potentiates inhibition of growth and migration in GBM cells and intracranial tumors. Financial SupportThis work was supported by R21 CA191444 (RBR), a Georgetown University Medical Center (GUMC) Dean for Researchs Toulmin Pilot Project Award (RBR), and a Partners in Research Breakthrough Award (RBR), as well as F99 CA234799 (DMT) and a student research grant from the Medical Center Graduate Student Organization (MCGSO, to DMT). Additional fellowship funding for DMT and MMH was provided by the Tumor Biology Training Grant (T32 CA009686, PI: Dr. Anna T. Riegel). Technical services were provided by the GUMC Animal Models, Flow Cytometry & Cell Sorting, Histopathology & Tissue, Microscopy & Imaging, and Tissue Culture Shared Resources, which are supported in part by Cancer Center Support Grant P30 CA051008 (PI: Dr. Louis M. Weiner). The Mayo Clinic Brain Tumor Patient-Derived Xenograft National Resource is supported in part by P50 CA108961 (JNS, PI: Dr. Patrick ONeill). The content of this article is the sole responsibility of the authors and does not represent the official views of the National Institutes of Health. Conflict of Interest and Author Contribution StatementThe authors declare no potential conflict of interest. DMT contributed to study design, performed experiments, analyzed data, and wrote the paper. SAK performed experiments, analyzed data, and wrote the paper. CJT performed experiments and analyzed data. MMH performed experiments. SDD performed experiments. JNS provided patient-derived xenograft samples. EG contributed to study design, and performed experiments. RBR contributed to study design, performed experiments, analyzed data, and wrote the paper. All authors reviewed, edited, and approved the manuscript.

cancer biology↗