Enhancers of glp-1, a gene required for cell-signaling in Caenorhabditis elegans, define a set of genes required for germline development.

Abstract The distal tip cell (DTC) regulates the proliferation or differentiation choice in the Caenorhabditis elegans germline by an inductive mechanism. Cell signaling requires a putative receptor in the germline, encoded b y the glp-1 gene, and a putative signal from the DTC, encoded by the lag-2 gene. Both glp-1 and lag-2 belong to multigene gene families whose members are essential for cell signaling during development of various tissues in insects and vertebrates as well as C. elegans. Relatively little is known about how these pathways regulate cell fate choice. To identify additional genes involved in the glp-1 signaling pathway, we carried out screens for genetic enhancers of glp-1. We recovered mutations in five new genes, named ego (enhancer of glp-1), and two previously identified genes, lag-1 and glp-4, that strongly enhance a weak glp-1 loss-of-function phenotype in the germline. Ego mutations cause multiple phenotypes consistent with the idea that gene activity is required for more than one aspect of germline and, in some cases, somatic development. Based on genetic experiments, glp-1 appears to act upstream of ego-1 and ego-3. We discuss the possible functional relationships among these genes in light of their phenotypes and interactions with glp-1.

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A predicted membrane protein, TRA-2A, directs hermaphrodite development in Caenorhabditis elegans

Development ◽

10.1242/dev.121.9.2995 ◽

1995 ◽

Vol 121 (9) ◽

pp. 2995-3004 ◽

Cited By ~ 7

Author(s):

P.E. Kuwabara ◽

J. Kimble

Keyword(s):

Heat Shock ◽

Membrane Protein ◽

Cell Fate ◽

Loss Of Function ◽

Heat Shock Promoter ◽

Somatic Development ◽

C Elegans ◽

Cellular Domain ◽

Carboxy Terminal ◽

Necessary And Sufficient

The nematode C. elegans naturally develops as either an XO male or XX hermaphrodite. The sex-determining gene, tra-2, promotes hermaphrodite development in XX animals. This gene encodes a predicted membrane protein, named TRA-2A, which has been proposed to provide the primary feminising activity of the tra-2 locus. Here, we show that transgenic TRA-2A driven from a heat shock promoter can fully feminise the somatic tissues of XX tra-2 loss-of-function mutants, which would otherwise develop as male. TRA-2A is thus likely to provide a component of the tra-2 locus that is both necessary and sufficient to promote female somatic development. Transgenic TRA-2A driven by the heat shock promoter can also transform XO animals from male to self-fertile hermaphrodite. This result establishes the role of tra-2 as a developmental switch that controls somatic sexual cell fate. We show that a carboxy-terminal region of TRA-2A, predicted to be intra-cellular, can partially feminise XX tra-2 loss-of-function mutants and XO tra-2(+) males. We suggest that this intra-cellular domain of TRA-2A promotes hermaphrodite development by negatively regulating the FEM proteins.

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LET-711, the Caenorhabditis elegans NOT1 Ortholog, Is Required for Spindle Positioning and Regulation of Microtubule Length in Embryos

Molecular Biology of the Cell ◽

10.1091/mbc.e06-02-0107 ◽

2006 ◽

Vol 17 (11) ◽

pp. 4911-4924 ◽

Cited By ~ 18

Author(s):

Leah R. DeBella ◽

Adam Hayashi ◽

Lesilee S. Rose

Keyword(s):

Caenorhabditis Elegans ◽

Cell Fate ◽

Regulation Of Gene Expression ◽

Early Embryo ◽

Cell Cortex ◽

Loss Of Function ◽

Wild Type ◽

Spindle Positioning ◽

C Elegans ◽

Associated Proteins

Spindle positioning is essential for the segregation of cell fate determinants during asymmetric division, as well as for proper cellular arrangements during development. In Caenorhabditis elegans embryos, spindle positioning depends on interactions between the astral microtubules and the cell cortex. Here we show that let-711 is required for spindle positioning in the early embryo. Strong loss of let-711 function leads to sterility, whereas partial loss of function results in embryos with defects in the centration and rotation movements that position the first mitotic spindle. let-711 mutant embryos have longer microtubules that are more cold-stable than in wild type, a phenotype opposite to the short microtubule phenotype caused by mutations in the C. elegans XMAP215 homolog ZYG-9. Simultaneous reduction of both ZYG-9 and LET-711 can rescue the centration and rotation defects of both single mutants. let-711 mutant embryos also have larger than wild-type centrosomes at which higher levels of ZYG-9 accumulate compared with wild type. Molecular identification of LET-711 shows it to be an ortholog of NOT1, the core component of the CCR4/NOT complex, which plays roles in the negative regulation of gene expression at transcriptional and post-transcriptional levels in yeast, flies, and mammals. We therefore propose that LET-711 inhibits the expression of ZYG-9 and potentially other centrosome-associated proteins, in order to maintain normal centrosome size and microtubule dynamics during early embryonic divisions.

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Steroid hormones sulfatase inactivation extends lifespan and ameliorates age-related diseases

Nature Communications ◽

10.1038/s41467-020-20269-y ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Mercedes M. Pérez-Jiménez ◽

José M. Monje-Moreno ◽

Ana María Brokate-Llanos ◽

Mónica Venegas-Calerón ◽

Alicia Sánchez-García ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Caenorhabditis Elegans ◽

Protein Aggregation ◽

Steroid Hormones ◽

Sensory Neurons ◽

Environmental Cues ◽

Steroid Sulfatase ◽

Loss Of Function ◽

C Elegans ◽

Age Related

AbstractAging and fertility are two interconnected processes. From invertebrates to mammals, absence of the germline increases longevity. Here we show that loss of function of sul-2, the Caenorhabditis elegans steroid sulfatase (STS), raises the pool of sulfated steroid hormones, increases longevity and ameliorates protein aggregation diseases. This increased longevity requires factors involved in germline-mediated longevity (daf-16, daf-12, kri-1, tcer-1 and daf-36 genes) although sul-2 mutations do not affect fertility. Interestingly, sul-2 is only expressed in sensory neurons, suggesting a regulation of sulfated hormones state by environmental cues. Treatment with the specific STS inhibitor STX64, as well as with testosterone-derived sulfated hormones reproduces the longevity phenotype of sul-2 mutants. Remarkably, those treatments ameliorate protein aggregation diseases in C. elegans, and STX64 also Alzheimer’s disease in a mammalian model. These results open the possibility of reallocating steroid sulfatase inhibitors or derivates for the treatment of aging and aging related diseases.

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A Cuticle Collagen Encoded by the lon-3 Gene May Be a Target of TGF-β Signaling in Determining Caenorhabditis elegans Body Shape

Genetics ◽

10.1093/genetics/162.4.1631 ◽

2002 ◽

Vol 162 (4) ◽

pp. 1631-1639

Author(s):

Yo Suzuki ◽

Gail A Morris ◽

Min Han ◽

William B Wood

Keyword(s):

Caenorhabditis Elegans ◽

Body Shape ◽

Small Body ◽

Dependent Manner ◽

Loss Of Function ◽

Cellular Mechanisms ◽

C Elegans ◽

Gene Expression Analyses ◽

Dose Dependent

Abstract The signaling pathway initiated by the TGF-β family member DBL-1 in Caenorhabditis elegans controls body shape in a dose-dependent manner. Loss-of-function (lf) mutations in the dbl-1 gene cause a short, small body (Sma phenotype), whereas overexpression of dbl-1 causes a long body (Lon phenotype). To understand the cellular mechanisms underlying these phenotypes, we have isolated suppressors of the Sma phenotype resulting from a dbl-1(lf) mutation. Two of these suppressors are mutations in the lon-3 gene, of which four additional alleles are known. We show that lon-3 encodes a collagen that is a component of the C. elegans cuticle. Genetic and reporter-gene expression analyses suggest that lon-3 is involved in determination of body shape and is post-transcriptionally regulated by the dbl-1 pathway. These results support the possibility that TGF-β signaling controls C. elegans body shape by regulating cuticle composition.

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glp-3 Is Required for Mitosis and Meiosis in the Caenorhabditis elegans Germ Line

Genetics ◽

10.1093/genetics/145.1.111 ◽

1997 ◽

Vol 145 (1) ◽

pp. 111-121 ◽

Cited By ~ 1

Author(s):

Lisa C Kadyk ◽

Eric J Lambie ◽

Judith Kimble

Keyword(s):

Caenorhabditis Elegans ◽

Germ Cells ◽

Germ Line ◽

Stem Cell Population ◽

Phenotypic Characterization ◽

Loss Of Function ◽

Dapi Staining ◽

Cell Cycles ◽

C Elegans ◽

Mitosis And Meiosis

The germ line is the only tissue in Caenorhabditis elegans in which a stem cell population continues to divide mitotically throughout life; hence the cell cycles of the germ line and the soma are regulated differently. Here we report the genetic and phenotypic characterization of the glp-3 gene. In animals homozygous for each of five recessive loss-of-function alleles, germ cells in both hermaphrodites and males fail to progress through mitosis and meiosis, but somatic cells appear to divide normally. Germ cells in animals grown at 15° appear by DAPI staining to be uniformly arrested at the G2/M transition with <20 germ cells per gonad on average, suggesting a checkpoint-mediated arrest. In contrast, germ cells in mutant animals grown at 25° frequently proliferate slowly during adulthood, eventually forming small germ lines with several hundred germ cells. Nevertheless, cells in these small germ lines never undergo meiosis. Double mutant analysis with mutations in other genes affecting germ cell proliferation supports the idea that glp-3 may encode a gene product that is required for the mitotic and meiotic cell cycles in the C. elegans germ line.

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Goα Regulates Volatile Anesthetic Action in Caenorhabditis elegans

Genetics ◽

10.1093/genetics/158.2.643 ◽

2001 ◽

Vol 158 (2) ◽

pp. 643-655 ◽

Cited By ~ 1

Author(s):

Bruno van Swinderen ◽

Laura B Metz ◽

Laynie D Shebester ◽

Jane E Mendel ◽

Paul W Sternberg ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Novel Mutation ◽

Volatile Anesthetic ◽

Loss Of Function ◽

Wild Type ◽

Α Subunit ◽

C Elegans ◽

Missense Mutant ◽

Anesthetic Action ◽

Mutant Phenotypes

Abstract To identify genes controlling volatile anesthetic (VA) action, we have screened through existing Caenorhabditis elegans mutants and found that strains with a reduction in Go signaling are VA resistant. Loss-of-function mutants of the gene goa-1, which codes for the α-subunit of Go, have EC50s for the VA isoflurane of 1.7- to 2.4-fold that of wild type. Strains overexpressing egl-10, which codes for an RGS protein negatively regulating goa-1, are also isoflurane resistant. However, sensitivity to halothane, a structurally distinct VA, is differentially affected by Go pathway mutants. The RGS overexpressing strains, a goa-1 missense mutant found to carry a novel mutation near the GTP-binding domain, and eat-16(rf) mutants, which suppress goa-1(gf) mutations, are all halothane resistant; goa-1(null) mutants have wild-type sensitivities. Double mutant strains carrying mutations in both goa-1 and unc-64, which codes for a neuronal syntaxin previously found to regulate VA sensitivity, show that the syntaxin mutant phenotypes depend in part on goa-1 expression. Pharmacological assays using the cholinesterase inhibitor aldicarb suggest that VAs and GOA-1 similarly downregulate cholinergic neurotransmitter release in C. elegans. Thus, the mechanism of action of VAs in C. elegans is regulated by Goα, and presynaptic Goα-effectors are candidate VA molecular targets.

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Genetic control of programmed cell death in the Caenorhabditis elegans hermaphrodite germline

Development ◽

10.1242/dev.126.5.1011 ◽

1999 ◽

Vol 126 (5) ◽

pp. 1011-1022 ◽

Cited By ~ 8

Author(s):

T.L. Gumienny ◽

E. Lambie ◽

E. Hartwieg ◽

H.R. Horvitz ◽

M.O. Hengartner

Keyword(s):

Cell Death ◽

Caenorhabditis Elegans ◽

Germ Cell ◽

Somatic Cell ◽

Cell Fate ◽

Germ Cells ◽

Mapk Pathway ◽

Apoptotic Cell ◽

C Elegans ◽

Pathway Activation

Development of the nematode Caenorhabditis elegans is highly reproducible and the fate of every somatic cell has been reported. We describe here a previously uncharacterized cell fate in C. elegans: we show that germ cells, which in hermaphrodites can differentiate into sperm and oocytes, also undergo apoptotic cell death. In adult hermaphrodites, over 300 germ cells die, using the same apoptotic execution machinery (ced-3, ced-4 and ced-9) as the previously described 131 somatic cell deaths. However, this machinery is activated by a distinct pathway, as loss of egl-1 function, which inhibits somatic cell death, does not affect germ cell apoptosis. Germ cell death requires ras/MAPK pathway activation and is used to maintain germline homeostasis. We suggest that apoptosis eliminates excess germ cells that acted as nurse cells to provide cytoplasmic components to maturing oocytes.

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Screening for Presenilin Inhibitors Using the Free-Living Nematode, Caenorhabditis elegans

CrossRef Listing of Deleted DOIs ◽

10.1177/1087057103261038 ◽

2004 ◽

Vol 9 (2) ◽

pp. 147-152 ◽

Cited By ~ 19

Author(s):

Brenda R. Ellerbrock ◽

Eileen M. Coscarelli ◽

Mark E. Gurney ◽

Timothy G. Geary

Keyword(s):

Caenorhabditis Elegans ◽

High Throughput Screening ◽

Screening Method ◽

Genetic System ◽

Body Cavity ◽

Egg Laying ◽

The Body ◽

Loss Of Function ◽

C Elegans ◽

Automated Method

Caenorhabditis elegans contains 3 homologs of presenilin genes that are associated with Alzheimer s disease. Loss-of-function mutations in C. elegans genes cause a defect in egg laying. In humans, loss of presenilin-1 (PS1) function reduces amyloid-beta peptide processing from the amyloid protein precursor. Worms were screened for compounds that block egg laying, phenocopying presenilin loss of function. To accommodate even relatively high throughput screening, a semi-automated method to quantify egg laying was devised by measuring the chitinase released into the culture medium. Chitinase is released by hatching eggs, but little is shed into the medium from the body cavity of a hermaphrodite with an egg laying deficient ( egl) phenotype. Assay validation involved measuring chitinase release from wild-type C. elegans (N2 strain), sel-12 presenilin loss-of-function mutants, and 2 strains of C. elegans with mutations in the egl-36K+ channel gene. Failure to find specific presenilin inhibitors in this collection likely reflects the small number of compounds tested, rather than a flaw in screening strategy. Absent defined biochemical pathways for presenilin, this screening method, which takes advantage of the genetic system available in C. elegans and its historical use for anthelminthic screening, permits an entry into mechanism-based discovery of drugs for Alzheimer s disease. ( Journal of Biomolecular Screening 2004:147-152)

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

Toxicology Research ◽

10.1039/c9tx00101h ◽

2019 ◽

Vol 8 (5) ◽

pp. 754-766 ◽

Cited By ~ 1

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.

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Caenorhabditis elegans as a Model Organism to Evaluate the Antioxidant Effects of Phytochemicals

Molecules ◽

10.3390/molecules25143194 ◽

2020 ◽

Vol 25 (14) ◽

pp. 3194

Author(s):

Begoña Ayuda-Durán ◽

Susana González-Manzano ◽

Ana M. González-Paramás ◽

Celestino Santos-Buelga

Keyword(s):

Oxidative Stress ◽

Caenorhabditis Elegans ◽

Model Organism ◽

Lipid Peroxides ◽

Biological Research ◽

Loss Of Function ◽

Fluorescent Reporters ◽

C Elegans ◽

High Degree

The nematode Caenorhabditis elegans was introduced as a model organism in biological research by Sydney Brenner in the 1970s. Since then, it has been increasingly used for investigating processes such as ageing, oxidative stress, neurodegeneration, or inflammation, for which there is a high degree of homology between C. elegans and human pathways, so that the worm offers promising possibilities to study mechanisms of action and effects of phytochemicals of foods and plants. In this paper, the genes and pathways regulating oxidative stress in C. elegans are discussed, as well as the methodological approaches used for their evaluation in the worm. In particular, the following aspects are reviewed: the use of stress assays, determination of chemical and biochemical markers (e.g., ROS, carbonylated proteins, lipid peroxides or altered DNA), influence on gene expression and the employment of mutant worm strains, either carrying loss-of-function mutations or fluorescent reporters, such as the GFP.

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