Biology subjects

Martin, S. L.

Publications and source records attributed to Martin, S. L..

10 recordsLinked to original sources

bioRxiv2026

Canonical insulin receptor/DAF-2 signaling-independent patterning and role for FoxO/DAF-16 in early embryos

Forkhead box O (FoxO) transcription factors (DAF-16 in Caenorhabditis elegans) regulate aging, metabolism, and development. Canonically, FoxO/DAF-16 activity is regulated by insulin/insulin-like receptor (DAF-2) signaling, which inhibits its nuclear localization. In C. elegans, strong loss-of-function daf-16; daf-2 double mutants are embryonic lethal. However, because daf-2 null mutants are maternally rescued as embryos and then arrest as larvae, the role of DAF-2 signaling in embryogenesis is unknown. We therefore used quantitative imaging and genetics to study DAF-16 and DAF-2 in early C. elegans embryos. DAF-16 was uniformly low in all nuclei at the 2- to 4-cell stage. From the 8- to 64-cell stage, DAF-16 became enriched in 1-2 nuclei of germ lineage cells. This patterning required germ fate determinants and the lipid phosphatase PTEN/DAF-18, but not DAF-2 kinase activity, and was independent of maternal age. We also found that daf-16; daf-2 double mutant embryos failed morphogenesis, with severe mitotic defects as early as the 1-cell stage. This work identifies germ lineage-specific DAF-16 patterning and a role for DAF-16 in early embryogenesis that is independent of canonical DAF-2 signaling.

developmental biology↗

bioRxiv2026

Genomic indicators of risk and resilience in global leatherback turtle populations

Understanding the drivers of genomic health and their consequences for population viability is often overlooked but potentially important to effective conservation amidst the biodiversity crisis of the Anthropocene. Leatherback turtle (Dermochelys coriacea) populations have declined globally due to anthropogenic factors, with some populations losing over 90% of their abundance over the past 30-50 years. While conservation efforts have been successful in stabilizing some populations, others continue to decline, and the reasons for these differential trajectories remain unclear. To assess how recent demographic factors, such as population size and decline, influence population genomic health, we combined population monitoring information with medium depth whole-genome and reduced representation resequencing data from globally representative populations. We found that small-stable populations have lower genomic diversity and higher inbreeding than large declining populations, reflecting prolonged small population sizes and limited gene flow. Yet, small-stable populations also show evidence of deleterious allele purging, suggesting genetic resilience. This, combined with lack of detectable genomic erosion over the study period, provides hope for potential recovery of healthy leatherback populations provided that anthropogenic threats are effectively mitigated. However, potential time lags and possible recent increases in inbreeding among close relatives in recently declined populations warrant continued monitoring and assessment. Genomic and abundance-based metrics were less aligned following rapid population declines, emphasizing the different timescales of the evolutionary and demographic processes they reflect, respectively, and the strength in their complementary, integrative use for extinction risk assessments. This also supports that it is not too late to turn the tide for recently declined leatherback populations and that continued investment in conservation efforts and threat reductions are warranted. Collectively, our results highlight how recent and historical demography shapes current genomic health and recovery potential in leatherback turtles, aids understanding of current risks and informs future conservation and management strategies.

ecology↗

bioRxiv2026

GPI lipid remodeling regulates lipophagy by forming lipid domains in response to glucose deprivation

Lipophagy is an important microautophagic process that degrades lipid droplets (LDs) to mobilize stored lipids as an energy source during nutrient starvation. However, the molecular mechanisms regulating lipophagy in response to nutrient starvation remain poorly understood. We found that budding yeast mutants defective in glycosylphosphatidylinositol (GPI) lipid remodeling exhibited aberrant accumulation of lipid droplets (LDs) and neutral lipids under glucose starvation. Our data suggest that the accumulation results from a failure of vacuolar liquid-ordered (Lo) domain-mediated lipophagy. Furthermore, we demonstrated that glycosylphosphatidylinositol-anchored proteins (GPI-APs) localize to vacuoles in response to glucose depletion and that a mutant defective in endocytosis has defects in both vacuolar Lo domain formation and lipophagy. These results imply that GPI lipid remodeling is required for Lo domain-mediated lipophagy upon glucose starvation. We propose that endocytosis functions to supply the lipid portion of GPI-APs, remodeled to C26 diacylglycerol, to the vacuolar membrane for Lo domain formation. Summary StatementOur data suggest that the endocytic transport of GPI-APs remodeled with C26 diacylglycerol to the vacuole is required for vacuolar Lo domain formation and subsequent lipophagy in response to glucose deprivation. This reveals the essential role of GPI lipid remodeling in ensuring lipophagy to adapt to changes in nutrient availability.

cell biology↗

bioRxiv2025

Sedimentary ancient DNA metagenomic analysis provides new insights into farming in central Norway from the Bronze Age to late Medieval period

Sedimentary ancient DNA (sedaDNA) has been proposed as a key methodology for reconstructing paleoclimates and biodiversity over time. To a lesser extent, it has been explored as a complementary tool for reconstructing human-driven local environmental changes over time, such as those explored in open air archaeological sites. Our study employs a sedaDNA metagenomic approach to investigate land use and environmental change at the archaeological site of Torg[a]rdsletta in central Norway, spanning from the Bronze Age through the Medieval period. Stratigraphic sediment samples reveal temporal shifts in plant, animal and microbial communities, reflecting evolving human practices and climatic conditions. Progression through the layers indicate signs or land clearance, cultivation and animal husbandry in the region. Notably, a significant reduction in microbial and plant diversity during periods of climatic upheaval--such as the AD 536-540 volcanic event--correlates with landscape and societal adjustments. The findings demonstrate that sedaDNA complements traditional proxies, providing high-resolution insights into past land use, environmental interactions, and societal organization. The successful extraction of ancient genetic material underscores sedaDNAs potential to reconstruct dynamic prehistoric landscapes and anthropogenic impacts, offering further potential for understanding long-term human-environment relationships in Scandinavia.

genomics↗

bioRxiv2024

Cell type-specific regulation by different cytokinetic pathways in the early embryo

Cytokinesis, the physical division of one cell into two, is typically assumed to use the same molecular process across animal cells. However, regulation of cell division can vary significantly among different cell types, even within the same multicellular organism. Using six fast-acting temperature-sensitive (ts) cytokinesis-defective mutants, we found that each had unique cell type-specific profiles in the early C. elegans embryo. Certain cell types were more sensitive than others to actomyosin and spindle signaling disruptions, disrupting two members of the same complex could result in different phenotypes, and protection against actomyosin inhibition did not always protect against spindle signaling inhibition.

cell biology↗

bioRxiv2024

Patterning, regulation, and role of FoxO/DAF-16 in the early embryo

Insulin resistance and diabetes are associated with many health issues including higher rates of birth defects and miscarriage during pregnancy. Because insulin resistance and diabetes are both associated with obesity, which also affects fertility, the role of insulin signaling itself in embryo development is not well understood. A key downstream target of the insulin/insulin-like growth factor signaling (IIS) pathway is the forkhead family transcription factor FoxO (DAF-16 in C. elegans). Here, we used quantitative live imaging to measure the patterning of endogenously tagged FoxO/DAF-16 in the early worm embryo. In 2-4-cell stage embryos, FoxO/DAF-16 initially localized uniformly to all cell nuclei, then became dramatically enriched in germ precursor cell nuclei beginning at the 8-cell stage. This nuclear enrichment in early germ precursor cells required germ fate specification, PI3K (AGE-1)- and PTEN (DAF-18)-mediated phospholipid regulation, and the deubiquitylase USP7 (MATH-33), yet was unexpectedly insulin receptor (DAF-2)- and AKT-independent. Functional analysis revealed that FoxO/DAF-16 acts as a cell cycle pacer for early cleavage divisions-without FoxO/DAF-16 cell cycles were shorter than in controls, especially in germ lineage cells. These results reveal the germ lineage specific patterning, upstream regulation, and cell cycle role for FoxO/DAF-16 during early C. elegans embryogenesis.

developmental biology↗

bioRxiv2023

Germ fate determinants protect germ precursor cell division by restricting septin and anillin levels at the division plane

Animal cell cytokinesis, or the physical division of one cell into two, is thought to be driven by constriction of an actomyosin contractile ring at the division plane. The mechanisms underlying cell type-specific differences in cytokinesis remain unknown. Germ cells are totipotent cells that pass genetic information to the next generation. Previously, using formincyk-1(ts) mutant C. elegans embryos, we found that the P2 germ precursor cell is protected from cytokinesis failure and can divide without detectable F-actin at the division plane. Here, we identified two canonical germ fate determinants required for P2-specific cytokinetic protection: PIE-1 and POS-1. Neither has been implicated previously in cytokinesis. These germ fate determinants protect P2 cytokinesis by reducing the accumulation of septinUNC-59 and anillinANI-1 at the division plane, which here act as negative regulators of cytokinesis. These findings may provide insight into cytokinetic regulation in other cell types, especially in stem cells with high potency.

cell biology↗

bioRxiv2021

Insights from the genomes of four diploid Camelina spp.

Plant evolution has been a complex process involving hybridization and polyploidization making understanding the origin and evolution of a plants genome challenging even once a published genome is available. The oilseed crop, Camelina sativa (Brassicaceae), has a fully sequenced allohexaploid genome with three unknown ancestors. To better understand which extant species best represent the ancestral genomes that contributed to C. sativas formation, we sequenced and assembled chromosome level draft genomes for four diploid members of Camelina: C. neglecta C. hispida var. hispida, C. hispida var. grandiflora and C. laxa using long and short read data scaffolded with proximity data. We then conducted phylogenetic analyses on regions of synteny and on genes described for Arabidopsis thaliana, from across each nuclear genome and the chloroplasts to examine evolutionary relationships within Camelina and Camelineae. We conclude that C. neglecta is closely related to C. sativas sub-genome 1 and that C. hispida var. hispida and C. hispida var. grandiflora are most closely related to C. sativas sub-genome 3. Further, the abundance and density of transposable elements, specifically Helitrons, suggest that the progenitor genome that contributed C. sativas sub-genome 3 maybe more similar to the genome of C. hispida var. hispida than that of C. hispida var. grandiflora. These diploid genomes show few structural differences when compared to C. sativas genome indicating little change to chromosome structure following allopolyploidization. This work also indicates that C. neglecta and C. hispida are important resources for understanding the genetics of C. sativa and potential resources for crop improvement.

genomics↗

bioRxiv2018

Dynamic temperature-sensitive A-to-I RNA editing in the brain of a heterothermic mammal during hibernation

RNA editing diversifies genomically encoded information to expand the complexity of the transcriptome. In ectothermic organisms, including Drosophila and Cephalopoda, where body temperature mirrors ambient temperature, decreases in environmental temperature lead to increases in A-to-I RNA editing and cause amino acid recoding events that are thought to be adaptive responses to temperature fluctuations. In contrast, endothermic mammals, including humans and mice, typically maintain a constant body temperature despite environmental changes. Here, A-to-I editing primarily targets repeat elements, rarely results in the recoding of amino acids and plays a critical role in innate immune tolerance. Hibernating ground squirrels provide a unique opportunity to examine RNA editing in a heterothermic mammal whose body temperature varies over 30{degrees}C and can be maintained at 5{degrees}C for many days during torpor. We profiled the transcriptome in three brain regions at six physiological states to quantify RNA editing and determine whether cold-induced RNA editing modifies the transcriptome as a potential mechanism for neuroprotection at low temperature during hibernation. We identified 5,165 A-to-I editing sites in 1,205 genes with dynamically increased editing after prolonged cold exposure. The majority (99.6%) of the cold-increased editing sites are outside of previously annotated coding regions, 82.7% lie in SINE-derived repeats, and 12 sites are predicted to recode amino acids. Additionally, A-to-I editing frequencies increase with increasing cold-exposure demonstrating that ADAR remains active during torpor. Our findings suggest that dynamic A-to-I editing at low body temperature may provide a neuroprotective mechanism to limit aberrant dsRNA accumulation during torpor in the mammalian hibernator.

genomics↗

bioRxiv2017

Genetic architecture drives seasonal onset of hibernation in the 13-lined ground squirrel

Hibernation is a highly dynamic phenotype whose timing, for many mammals, is controlled by a circannual clock and accompanied by rhythms in body mass and food intake. When housed in an animal facility, 13-lined ground squirrels exhibit individual variation in the seasonal onset of hibernation, which is not explained by environmental or biological factors, such as body mass and sex. We hypothesized that underlying genetic architecture instead drives variation in this timing. After first increasing the contiguity of the genome assembly, we therefore employed a genotype-by-sequencing approach to characterize genetic variation in 153 13-lined ground squirrels. Combining this with datalogger records, we estimated high heritability (61-100%) for the seasonal onset of hibernation. After applying a genome-wide scan with 46,996 variants, we also identified 21 loci significantly associated with hibernation immergence, which alone accounted for 54% of the variance in the phenotype. The most significant marker (SNP 15, p=3.81x10-6) was located near prolactin-releasing hormone receptor (PRLHR), a gene that regulates food intake and energy homeostasis. Other significant loci were located near genes functionally related to hibernation physiology, including muscarinic acetylcholine receptor M2 (CHRM2), involved in the control of heart rate, exocyst complex component 4 (EXOC4) and prohormone convertase 2 (PCSK2), both of which are involved in insulin signaling and processing. Finally, we applied an expression quantitative loci (eQTL) analysis using existing transcriptome datasets, and we identified significant (q<0.1) associations for 9/21 variants. Our results highlight the power of applying a genetic mapping strategy to hibernation and present new insight into the genetics driving its seasonal onset.

genetics↗