Changes in body shape implicate cuticle stretch in C. elegans growth control

Nyaanga, Joy; Goss, Christina; Zhang, Gaotian; Ahmed, Hannah N.; Andersen, Elliot J; Miller, Isabella R.; Rozenich, Justine K; Swarthout, Iris L.; Vaughn, Jordan  A.; Mangan, Niall M.; Shirman, Sasha; Andersen, Erik C.

doi:10.1016/j.cdev.2022.203780

Cited by 10 publications

(6 citation statements)

References 57 publications

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“…Fitness effects of resistance alleles in Caenorhabditis elegans avr-14 and avr-15 or the loss of three GluCl subunits (avr-14, avr-15, and glc-1) did not significantly differ in ivermectin response as previously reported in mutagenesis studies [82,84,85]. It is also critical to note that strains with a loss of both avr-14 and avr-15 or a loss of three GluCl subunits (avr-14, avr-15, and glc-1) have significant fitness consequences when not under ivermectin exposure, rendering it unlikely that loss-of-function mutations will occur in these genes and confer ivermectin resistance in nature.…”

Section: Plos Pathogenssupporting

confidence: 81%

“…Longer median animal length (i.e., larger animals) than the N2 strain corresponds to increased resistance to the tested drugs, and shorter median animal length (i.e., smaller animals) than the N2 strain corresponds to increased sensitivity to the tested drugs. Strains varied in length after growth for 48 hours in control conditions, but the loss of avr-14 and avr-15 caused the most significant delays in development (S6 Fig) . Despite substantial variation among strains in control (DMSO) conditions, animal measurements were categorized as the L4 larval stage by our custom CellProfiler worm models [82,83], indicating all strains underwent normal development in control conditions.…”

Section: Loss Of Ben-1 Conferred Albendazole Resistance and Loss Of B...mentioning

confidence: 99%

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Quantifying the fitness effects of resistance alleles with and without anthelmintic selection pressure using Caenorhabditis elegans

Shaver,

Miller,

Schaye

et al. 2024

PLoS Pathog

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Albendazole (a benzimidazole) and ivermectin (a macrocyclic lactone) are the two most commonly co-administered anthelmintic drugs in mass-drug administration programs worldwide. Despite emerging resistance, we do not fully understand the mechanisms of resistance to these drugs nor the consequences of delivering them in combination. Albendazole resistance has primarily been attributed to variation in the drug target, a beta-tubulin gene. Ivermectin targets glutamate-gated chloride channels (GluCls), but it is unknown whether GluCl genes are involved in ivermectin resistance in nature. Using Caenorhabditis elegans, we defined the fitness costs associated with loss of the drug target genes singly or in combinations of the genes that encode GluCl subunits. We quantified the loss-of-function effects on three traits: (i) multi-generational competitive fitness, (ii) fecundity, and (iii) development. In competitive fitness and development assays, we found that a deletion of the beta-tubulin gene ben-1 conferred albendazole resistance, but ivermectin resistance required the loss of two GluCl genes (avr-14 and avr-15). The fecundity assays revealed that loss of ben-1 did not provide any fitness benefit in albendazole conditions and that no GluCl deletion mutants were resistant to ivermectin. Next, we searched for evidence of multi-drug resistance across the three traits. Loss of ben-1 did not confer resistance to ivermectin, nor did loss of any single GluCl subunit or combination confer resistance to albendazole. Finally, we assessed the development of 124 C. elegans wild strains across six benzimidazoles and seven macrocyclic lactones to identify evidence of multi-drug resistance between the two drug classes and found a strong phenotypic correlation within a drug class but not across drug classes. Because each gene affects various aspects of nematode physiology, these results suggest that it is necessary to assess multiple fitness traits to evaluate how each gene contributes to anthelmintic resistance.

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Section: Plos Pathogenssupporting

confidence: 81%

Section: Loss Of Ben-1 Conferred Albendazole Resistance and Loss Of B...mentioning

confidence: 99%

Quantifying the fitness effects of resistance alleles with and without anthelmintic selection pressure using Caenorhabditis elegans

Shaver,

Miller,

Schaye

et al. 2024

PLoS Pathog

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“…S1C ) started ∼2 h earlier on male-conditioned plates (MCP), indicating that multiple aspects of reproductive development were accelerated about as much as the vulva. During larval development, C. elegans hermaphrodites increase in volume ∼100-fold ( Nyaanga et al, 2022 ; Stojanovski et al, 2022 ; Uppaluri and Brangwynne, 2015 ). We found that by the larva-to-adult transition, worms on MCP were larger than the controls ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Accelerated hermaphrodite maturation on male pheromones suggests a general principle of coordination between larval behavior and development

Faerberg,

Aprison,

Ruvinsky

2024

Development

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Environment in general and social signals in particular could alter development. In Caenorhabditis elegans, male pheromones hasten development of hermaphrodite larvae. We show that this involves acceleration of growth and both somatic and germline development during the last larval stage (L4). Larvae exposed to male pheromones spend more time in L3 and less in the quiescent period between L3 and L4. This behavioral alteration improves provision in early L4, likely allowing for faster development. Larvae must be exposed to male pheromones in late L3 for behavioral and developmental effects to occur. Latter portions of other larval stages also contain periods of heightened sensitivity to environmental signals. Behavior during the early part of the larval stages is biased toward exploration, whereas later the emphasis shifts to food consumption. We argue that this organization allows assessment of the environment to identify the most suitable patch of resources, followed by acquisition of sufficient nutrition and salient information for the developmental events in the next larval stage. Evidence from other species indicates that such coordination of behavior and development may be a general feature of larval development.

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“…Data for each well were summarized to obtain median well measurements. TOF and norm.EXT data were then converted to microns as previously described ( Nyaanga et al 2022 ).…”

Section: Methodsmentioning

confidence: 99%

Linkage mapping reveals loci that underlie differences in Caenorhabditis elegans growth

Nyaanga

Andersen

2022

G3 Genes|Genomes|Genetics

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Growth rate and body size are complex traits that contribute to the fitness of organisms. The identification of loci that underlie differences in these traits provides insights into the genetic contributions to development. Leveraging Caenorhabditis elegans as a tractable metazoan model for quantitative genetics, we can identify genomic regions that underlie differences in growth. We measured post-embryonic growth of the laboratory-adapted wild-type strain (N2) and a wild strain from Hawaii (CB4856), and found differences in body size. Using linkage mapping, we identified three distinct quantitative trait loci (QTL) on chromosomes IV, V, and X that are associated with variation in body growth. We further examined these growth-associated QTL using chromosome substitution strains and near-isogenic lines, and validated the chromosome X QTL. Additionally, we generated a list of candidate genes for the chromosome X QTL. These genes could potentially contribute to differences in animal growth and should be evaluated in subsequent studies. Our work reveals the genetic architecture underlying animal growth variation and highlights the genetic complexity of growth in C. elegans natural populations.

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Changes in body shape implicate cuticle stretch in C. elegans growth control

Cited by 10 publications

References 57 publications

Quantifying the fitness effects of resistance alleles with and without anthelmintic selection pressure using Caenorhabditis elegans

Quantifying the fitness effects of resistance alleles with and without anthelmintic selection pressure using Caenorhabditis elegans

Accelerated hermaphrodite maturation on male pheromones suggests a general principle of coordination between larval behavior and development

Linkage mapping reveals loci that underlie differences in Caenorhabditis elegans growth

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