scholarly journals Genetic analysis of Caenorhabditis elegans pry-1/Axin suppressors identifies genes involved in reproductive structure development, stress responses, and aging

2021 ◽  
Author(s):  
Avijit Mallick ◽  
Nikita Jhaveri ◽  
Jihae Jeon ◽  
Yvonne Chang ◽  
Krupali Shah ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Stress Response ◽  
Stress Responses ◽  
Genetic Interaction ◽  
Gene Families ◽  
Genetic Network ◽  
Reproductive Structure ◽  
Structure Development ◽  
Developmental Processes ◽  
C Elegans

Abstract The Axin family of scaffolding proteins regulates a wide array of developmental and post-developmental processes in eukaryotes. Studies in the nematode Caenorhabditis elegans have shown that the Axin homolog PRY-1 plays essential roles in multiple tissues. To understand the genetic network of pry-1, we focused on a set of genes that are differentially expressed in the pry-1-mutant transcriptome and are linked to reproductive structure development. Knocking down eight of the genes (spp-1, clsp-1, ard-1, rpn-7, cpz-1, his-7, cdk-1, and rnr-1) via RNA interference efficiently suppressed the multivulva phenotype of pry-1 mutants. In all cases, the ectopic induction of P3.p vulval precursor cell was also inhibited. The suppressor genes are members of known gene families in eukaryotes and perform essential functions. Our genetic interaction experiments revealed that in addition to their role in vulval development, these genes participate in one or more pry-1-mediated biological events. Whereas four of them (cpz-1, his-7, cdk-1, and rnr-1) function in both stress response and aging, two (spp-1 and ard-1) are specific to stress response. Altogether, these findings demonstrate the important role of pry-1 suppressors in regulating developmental and post-developmental processes in C. elegans. Given that the genes described in this study are conserved, future investigations of their interactions with Axin and their functional specificity promises to uncover the genetic network of Axin in metazoans.

scholarly journals Genetic analysis of Caenorhabditis elegans pry-1/Axin suppressors identifies genes involved in reproductive structure development, stress response, and aging

2021 ◽  
Author(s):  
Avijit Mallick ◽  
Nikita Jhaveri ◽  
Jihae Jeon ◽  
Yvonne Chang ◽  
Krupali Shah ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Stress Response ◽  
Genetic Interaction ◽  
Gene Families ◽  
Genetic Network ◽  
Reproductive Structure ◽  
Structure Development ◽  
C Elegans ◽  
Disease States ◽  
Genetic Epistasis

The Axin family of scaffolding proteins regulates a wide array of developmental and post-developmental processes in eukaryotes. Studies in the nematode, Caenorhabditis elegans, have shown that the Axin homolog, PRY-1, plays essential roles in multiple tissues. To understand the genetic network of pry-1, we focused on a set of genes that are differentially expressed in the pry-1-mutant transcriptome and are linked to reproductive structure development. Eight of the genes (ard-1, rpn-7, cpz-1, his-7, cdk-1, rnr-1, clsp-1, and spp-1), when knocked down by RNA interference, efficiently suppressed the plate-level multivulva phenotype of pry-1 mutants. In every case, other than clsp-1 and spp-1, the ectopic vulval precursor cell (VPC) induction was also inhibited. The suppressor genes are members of known gene families in eukaryotes and perform essential functions. Our genetic interaction experiments revealed that except for clsp-1, the genes participate in one or more pry-1-mediated biological events. While four of them (cpz-1, his-7, cdk-1, and rnr-1) function in VPC induction, stress response, and aging, the other three (spp-1, ard-1, and rpn-7) are specific to one or more of these processes. Further analysis of the genes involved in aging showed that his-7, cdk-1, and rnr-1 also interacted with daf-16/FOXO. The results of genetic epistasis experiments suggested that his-7 functions upstream of daf-16, whereas cdk-1and rnr-1 act downstream of the pry-1-daf-16 pathway. Altogether, these findings demonstrate the important role of pry-1 suppressors in C. elegans. Given that all of the genes described in this study are conserved, future investigations of their interactions with Axin and their functional specificity promises to uncover the genetic network of Axin under normal and disease states.

scholarly journals Specific microRNAs Regulate Heat Stress Responses in Caenorhabditis elegans

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Camilla Nehammer ◽  
Agnieszka Podolska ◽  
Sebastian D. Mackowiak ◽  
Konstantinos Kagias ◽  
Roger Pocock
Keyword(s):  
Heat Stress ◽  
Caenorhabditis Elegans ◽  
Stress Response ◽  
Stress Responses ◽  
Posttranscriptional Regulation ◽  
Transcriptional Control ◽  
Heat Stress Response ◽  
C Elegans ◽  
Additional Layer ◽  
Sense And Respond

Abstract The ability of animals to sense and respond to elevated temperature is essential for survival. Transcriptional control of the heat stress response has been much studied, whereas its posttranscriptional regulation by microRNAs (miRNAs) is not well understood. Here we analyzed the miRNA response to heat stress in Caenorhabditis elegans and show that a discrete subset of miRNAs is thermoregulated. Using in-depth phenotypic analyses of miRNA deletion mutant strains we reveal multiple developmental and post-developmental survival and behavioral functions for specific miRNAs during heat stress. We have identified additional functions for already known players (mir-71 and mir-239) as well as identifying mir-80 and the mir-229 mir-64-66 cluster as important regulators of the heat stress response in C. elegans. These findings uncover an additional layer of complexity to the regulation of stress signaling that enables animals to robustly respond to the changing environment.

Rubidium chloride increases lifespan through an AMPK/FOXO-dependent pathway in Caenorhabditis elegans

2021 ◽  
Author(s):  
Mengjiao Hao ◽  
Zhikang Zhang ◽  
Yijun Guo ◽  
Huihao Zhou ◽  
Qiong Gu ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Stress Responses ◽  
Aging Effect ◽  
Stress Effect ◽  
Neuroprotective Effects ◽  
C Elegans ◽  
Cycle Arrest ◽  
Age Related ◽  
Promising Target ◽  
Amp Activated Protein Kinase

Abstract AMP-activated protein kinase (AMPK) is involved in life span maintenance, stress responses, and germ cell cycle arrest upon dauer entry. AMPK is currently considered a promising target for preventing age-related diseases. Rubidium is one of the trace elements in human body. As early as the 1970s, RbCl has been was reported to have neuroprotective effects. In this work, we report the anti-aging effect of RbCl in Caenorhabditis elegans. Specifically, we reveal that (1) RbCl does increase the lifespan and enhance stress resistance in C. elegans without disturbing their fecundity. (2) RbCl induces superoxide dismutase (SOD) expression, which is essential for its anti-aging and anti-stress effect. (3) AAK-2 and DAF-16 are essential to the anti-aging efficacy of RbCl, and RbCl can promote DAF-16 translocating into the nucleus, suggesting that RbCl delays aging through regulating AMPK/FOXO pathway. RbCl can be a promising agent against aging related diseases.

scholarly journals In the Model Host Caenorhabditis elegans, Sphingosine-1-Phosphate-Mediated Signaling Increases Immunity toward Human Opportunistic Bacteria

2020 ◽  
Vol 21 (21) ◽  
pp. 7813
Author(s):  
Kiho Lee ◽  
Iliana Escobar ◽  
Yeeun Jang ◽  
Wooseong Kim ◽  
Frederick M. Ausubel ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Stress Responses ◽  
Mapk Signaling ◽  
Dependent Manner ◽  
Cellular Functions ◽  
Kinase Gene ◽  
Concentration Dependent Manner ◽  
C Elegans ◽  
Opportunistic Bacteria ◽  
Free Living Nematode

Sphingosine-1-phophate (S1P) is a sphingolipid-derived signaling molecule that controls diverse cellular functions including cell growth, homeostasis, and stress responses. In a variety of metazoans, cytosolic S1P is transported into the extracellular space where it activates S1P receptors in a concentration-dependent manner. In the free-living nematode Caenorhabditis elegans, the spin-2 gene, which encodes a S1P transporter, is activated during Gram-positive or Gram-negative bacterial infection of the intestine. However, the role during infection of spin-2 and three additional genes in the C. elegans genome encoding other putative S1P transporters has not been elucidated. Here, we report an evolutionally conserved function for S1P and a non-canonical role for S1P transporters in the C. elegans immune response to bacterial pathogens. We found that mutations in the sphingosine kinase gene (sphk-1) or in the S1P transporter genes spin-2 or spin-3 decreased nematode survival after infection with Pseudomonas aeruginosa or Enterococcus faecalis. In contrast to spin-2 and spin-3, mutating spin-1 leads to an increase in resistance to P. aeruginosa. Consistent with these results, when wild-type C. elegans were supplemented with extracellular S1P, we found an increase in their lifespan when challenged with P. aeruginosa and E. faecalis. In comparison, spin-2 and spin-3 mutations suppressed the ability of S1P to rescue the worms from pathogen-mediated killing, whereas the spin-1 mutation had no effect on the immune-enhancing activity of S1P. S1P demonstrated no antimicrobial activity toward P. aeruginosa and Escherichia coli and only minimal activity against E. faecalis MMH594 (40 µM). These data suggest that spin-2 and spin-3, on the one hand, and spin-1, on the other hand, transport S1P across cellular membranes in opposite directions. Finally, the immune modulatory effect of S1P was diminished in C. eleganssek-1 and pmk-1 mutants, suggesting that the immunomodulatory effects of S1P are mediated by the p38 MAPK signaling pathway.

scholarly journals In vivo analysis of FANCD2 recruitment at meiotic DNA breaks in Caenorhabditis elegans

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Marcello Germoglio ◽  
Anna Valenti ◽  
Ines Gallo ◽  
Chiara Forenza ◽  
Pamela Santonicola ◽  
...  
Keyword(s):  
Dna Repair ◽  
Caenorhabditis Elegans ◽  
Genome Stability ◽  
Genetic Interaction ◽  
Model Systems ◽  
Dna Breaks ◽  
Strand Breaks ◽  
C Elegans ◽  
In Vivo Analysis

AbstractFanconi Anemia is a rare genetic disease associated with DNA repair defects, congenital abnormalities and infertility. Most of FA pathway is evolutionary conserved, allowing dissection and mechanistic studies in simpler model systems such as Caenorhabditis elegans. In the present study, we employed C. elegans to better understand the role of FA group D2 (FANCD2) protein in vivo, a key player in promoting genome stability. We report that localization of FCD-2/FANCD2 is dynamic during meiotic prophase I and requires its heterodimeric partner FNCI-1/FANCI. Strikingly, we found that FCD-2 recruitment depends on SPO-11-induced double-strand breaks (DSBs) but not RAD-51-mediated strand invasion. Furthermore, exposure to DNA damage-inducing agents boosts FCD-2 recruitment on the chromatin. Finally, analysis of genetic interaction between FCD-2 and BRC-1 (the C. elegans orthologue of mammalian BRCA1) supports a role for these proteins in different DSB repair pathways. Collectively, we showed a direct involvement of FCD-2 at DSBs and speculate on its function in driving meiotic DNA repair.

scholarly journals High-throughput transcriptome sequencing reveals extremely high doses of ionizing radiation-response genes in Caenorhabditis elegans

2019 ◽  
Vol 8 (5) ◽  
pp. 754-766 ◽  
Author(s):  
Youqin Xu ◽  
Lina Chen ◽  
Mengyi Liu ◽  
Yanfang Lu ◽  
Yanwei Yue ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Ionizing Radiation ◽  
Differential Expression ◽  
Gene Families ◽  
Rna Degradation ◽  
Cellular Growth ◽  
Radiation Response ◽  
Signalling Pathways ◽  
C Elegans ◽  
High Doses

Abstract This study sought novel ionizing radiation-response (IR-response) genes in Caenorhabditis elegans (C. elegans). C. elegans was divided into three groups and exposed to different high doses of IR: 0 gray (Gy), 200 Gy, and 400 Gy. Total RNA was extracted from each group and sequenced. When the transcriptomes were compared among these groups, many genes were shown to be differentially expressed, and these genes were significantly enriched in IR-related biological processes and pathways, including gene ontology (GO) terms related to cellular behaviours, cellular growth and purine metabolism and kyoto encyclopedia of genes and genomes (KEGG) pathways related to ATP binding, GTPase regulator activity, and RNA degradation. Quantitative reverse-transcription PCR (qRT-PCR) confirmed that these genes displayed differential expression across the treatments. Further gene network analysis showed a cluster of novel gene families, such as the guanylate cyclase (GCY), Sm-like protein (LSM), diacylglycerol kinase (DGK), skp1-related protein (SKR), and glutathione S-transferase (GST) gene families which were upregulated. Thus, these genes likely play important roles in IR response. Meanwhile, some important genes that are well known to be involved in key signalling pathways, such as phosphoinositide-specific phospholipase C-3 (PLC-3), phosphatidylinositol 3-kinase age-1 (AGE-1), Raf homolog serine/threonine-protein kinase (LIN-45) and protein cbp-1 (CBP-1), also showed differential expression during IR response, suggesting that IR response might perturb these key signalling pathways. Our study revealed a series of novel IR-response genes in Caenorhabditis elegans that might act as regulators of IR response and represent promising markers of IR exposure.

scholarly journals A Hot Water Extract of Sideritis scardica Prolongs Life Span and Enhances Heat Shock Resistance in Caenorhabditis elegans

2020 ◽  
Vol 15 (4) ◽  
pp. 1934578X2091728
Author(s):  
Yoshihiko Nishioka ◽  
Seiya Nishikawa ◽  
Toshiyuki Shibata
Keyword(s):  
Heat Stress ◽  
Caenorhabditis Elegans ◽  
Stress Response ◽  
Heat Shock ◽  
Life Span ◽  
Water Extract ◽  
Hot Water ◽  
Control Group ◽  
C Elegans ◽  
Hot Water Extract

Sideritis scardica is a Lamiaceae plant that is endemic to the alpine zone of the Balkan Peninsula. The tea of S. scardica has been handed down as a “tea of longevity” in the Rhodope region of Bulgaria for an unknown amount of time. In this study, we prepared a hot water extract of S. scardica (SHWE) and examined its effects on both life span and stress response in living tissue using Caenorhabditis elegans and its transgenic mutants. The life span of wild-type N2 worms was prolonged by approximately 15% at the SHWE concentration of 5 µg/mL and approximately 22% at the SHWE concentration of 50 µg/mL, as compared with the control group. The effect of SHWE on the expression of heat shock protein 16.2 (HSP-16.2) under heat stress was investigated using TJ375 worms, a transgenic mutant of C. elegans. In the TJ375 worms pretreated with SHWE, the fluorescence intensity of green fluorescent protein fluorescence, which indicates the expression of HSP-16.2, was significantly increased. In the assay using TJ356 worms, the worms pretreated with SHWE did not show the translocation of DAF-16, a forkhead transcription factor class O homolog, from the cytoplasm to nucleus under heat stress. Additionally, under heat stress, the pretreatment of SHWE improved the survival rate of GR1307 worms, a knockout mutant of daf-16. These results indicate that SHWE enhances HSP-16.2 expression through a stress-response pathway (eg, HSF-1 pathway) other than the DAF-16 pathway, resulting in a prolonged life span of C. elegans under heat stress.

scholarly journals The Caenorhabditis elegans rol-6 gene, which interacts with the sqt-1 collagen gene to determine organismal morphology, encodes a collagen.

1990 ◽  
Vol 10 (5) ◽  
pp. 2081-2089 ◽  
Author(s):  
J M Kramer ◽  
R P French ◽  
E C Park ◽  
J J Johnson
Keyword(s):  
Caenorhabditis Elegans ◽  
Restriction Site ◽  
Genetic Interaction ◽  
The Other ◽  
C Elegans ◽  
Allele Specific ◽  
Specific Restriction ◽  
The Right ◽  
Sequence Similarities ◽  
Dominant Suppressor

The rol-6 gene is one of the more than 40 loci in Caenorhabditis elegans that primarily affect organismal morphology. Certain mutations in the rol-6 gene produce animals that have the right roller phenotype, i.e., they are twisted into a right-handed helix. The rol-6 gene interacts with another gene that affects morphology, sqt-1; a left roller allele of sqt-1 acts as a dominant suppressor of a right roller allele of rol-6. The sqt-1 gene has previously been shown to encode a collagen. We isolated and sequenced the rol-6 gene and found that it also encodes a collagen. The rol-6 gene was identified by physical mapping of overlapping chromosomal deficiencies that cover the gene and by identification of an allele-specific restriction site alteration. The amino acid sequence of the collagen encoded by rol-6 is more similar to that of the sqt-1 collagen than to any of the other ten C. elegans cuticle collagen sequences compared. The locations of cysteine residues flanking the Gly-X-Y repeat regions of rol-6 and sqt-1 are identical, but differ from those in the other collagens. The sequence similarities between rol-6 and sqt-1 indicate that they represent a new collagen subfamily in C. elegans. These findings suggest that these two collagens physically interact, possibly explaining the genetic interaction seen between the rol-6 and sqt-1 genes.

Characterization of the xenobiotic response of Caenorhabditis elegans to the anthelmintic drug albendazole and the identification of novel drug glucoside metabolites

2010 ◽  
Vol 432 (3) ◽  
pp. 505-516 ◽  
Author(s):  
Steven T. Laing ◽  
Al Ivens ◽  
Roz Laing ◽  
Sai Ravikumar ◽  
Victoria Butler ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Stress Responses ◽  
Transcriptional Response ◽  
Metabolizing Enzymes ◽  
C Elegans ◽  
Genes Encoding ◽  
Minimal Importance ◽  
Xenobiotic Response ◽  
Novel Drug ◽  
Anthelmintic Drugs

Knowledge of how anthelmintics are metabolized and excreted in nematodes is an integral part of understanding the factors that determine their potency, spectrum of activity and for investigating mechanisms of resistance. Although there is remarkably little information on these processes in nematodes, it is often suggested that they are of minimal importance for the major anthelmintic drugs. Consequently, we have investigated how the model nematode Caenorhabditis elegans responds to and metabolizes albendazole, one of the most important anthelmintic drugs for human and animal use. Using a mutant strain lacking the β-tubulin drug target to minimize generalized stress responses, we show that the transcriptional response is dominated by genes encoding XMEs (xenobiotic-metabolizing enzymes), particularly cytochrome P450s and UGTs (UDP-glucuronosyl transferases). The most highly induced genes are predominantly expressed in the worm intestine, supporting their role in drug metabolism. HPLC-MS/MS revealed the production of two novel glucoside metabolites in C. elegans identifying a major difference in the biotransformation of this drug between nematodes and mammals. This is the first demonstration of metabolism of a therapeutic anthelmintic in C. elegans and provides a framework for its use to functionally investigate nematode anthelmintic metabolism.

scholarly journals The Atypical Rho GTPase CHW-1 Works With SAX-3/Robo to Mediate Axon Guidance in Caenorhabditis elegans

2018 ◽  
Author(s):  
Jamie K. Alan ◽  
Sara Robinson ◽  
Katie Magsig ◽  
Rafael S. Demarco ◽  
Erik A. Lundquist
Keyword(s):  
Caenorhabditis Elegans ◽  
Axon Guidance ◽  
Motor Neurons ◽  
Rho Gtpases ◽  
Rho Gtpase ◽  
Genetic Interaction ◽  
Small Gtpases ◽  
Axon Pathfinding ◽  
Rho Proteins ◽  
C Elegans

AbstractDuring development, neuronal cells extend an axon towards their target destination in response to a cue to form a properly functioning nervous system. Rho proteins, Ras-related small GTPases that regulate cytoskeletal organization and dynamics, cell adhesion, and motility, are known to regulate axon guidance. Despite extensive knowledge about canonical Rho proteins (RhoA/Rac1/Cdc42), little is known about the Caenorhabditis elegans (C. elegans) atypical Cdc42-like family members CHW-1 and CRP-1 in regards to axon pathfinding and neuronal migration. chw-1(Chp/Wrch) encodes a protein that resembles human Chp (Wrch-2/RhoV) and Wrch-1 (RhoU), and crp-1 encodes for a protein that resembles TC10 and TCL. Here, we show that chw-1 works redundantly with crp-1 and cdc-42 in axon guidance. Furthermore, proper levels of chw-1 expression and activity are required for proper axon guidance. When examining CHW-1 GTPase mutants, we found that the native CHW-1 protein is likely partially activated, and mutations at a conserved residue (position 12 using Ras numbering, position 18 in CHW-1) alter axon guidance and neural migration. Additionally, we showed that chw-1 genetically interacts with the guidance receptor sax-3 in PDE neurons. Finally, in VD/DD motor neurons, chw-1 works downstream of sax-3 to control axon guidance. In summary, this is the first study implicating the atypical Rho GTPases chw-1 and crp-1 in axon guidance. Furthermore, this is the first evidence of genetic interaction between chw-1 and the guidance receptor sax-3. These data suggest that chw-1 is likely acting downstream and/or in parallel to sax-3 in axon guidance.

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