1. Baldwin, J.G., Nadler, S.A., and Wall, D.H. 1997. Nematodes: Pervading the Earth and Linking all Life. Pp. 176-191. In: Raven, P.H. (ed.). National Academy Press, Washington, D.C. 625 pp.. 2. Bargmann, C. I. 1998. Neurobiology of the Caenorhabditis elegans genome. Science 282:2028-2033.. 3. Bargmann, C. I. And Mori, I. 1997. Chemotaxis and Thermotaxis. Pp. 717-737. In: Riddle, D.L., Blumenthal, T., Meyer, B.J. and Priess, J.R. (eds). C. elegans II. Cold Spring Harbor Laboratory Press, Plainview, NY 1222 pp.. 4. Bird, D.M. and Opperman, C. H. 1998. Caenorhabditis elegans. J. Nematol. 30:299-308.. 5. Bird, D.M., Opperman, C.H., Jones S.J.M., and Baillie, D.L. 1999. The Caenorhabditis elegans gemome: a guide in the post genomics age. Annu. Rev. Phytopathol. 37:247-265.. 6. Blaxter, M. 1998. Caenorhabditis elegans is a nematode. Science 282:2041-2046.. 7. Blaxter, M. and Bird, D. 1997. Parasitic nematodes. Pp. 851-878. In: Riddle, D.L., Blumenthal, T., Meyer, B.J. and Priess, J.R. (eds). C. ...
WormBase is an online biological database about the biology and genome of the nematode model organism Caenorhabditis elegans and contains information about other related nematodes. WormBase is used by the C. elegans research community both as an information resource and as a place to publish and distribute their results. The database is regularly updated with new versions being released every two months. WormBase is one of the organizations participating in the Generic Model Organism Database (GMOD) project. WormBase comprises the following main data sets: The annotated genomes of Caenorhabditis elegans, Caenorhabditis briggsae, Caenorhabditis remanei, Caenorhabditis brenneri, Caenorhabditis angaria, Pristionchus pacificus, Haemonchus contortus, Meloidogyne hapla, Meloidogyne incognita, Brugia malayi and Onchocerca volvulus; Hand-curated annotations describing the function of ~20,500 C. elegans protein-coding genes and ~16,000 C. elegans non-coding genes; Gene families; Orthologies; Genomic ...
The molecular mechanisms underlying muscle atrophy during spaceflight are not well understood. We have analyzed the effects of a 10-day spaceflight on Caenorhabditis elegans muscle development. DNA microarray, real-time quantitative PCR, and quantitative western blot analyses revealed that the amount of MHC in both body-wall and pharyngeal muscle decrease in response to spaceflight. Decreased transcription of the body-wall myogenic transcription factor HLH-1 (CeMyoD) and of the three pharyngeal myogenic transcription factors, PEB-1, CEH-22 and PHA-4 were also observed. Upon return to Earth animals displayed reduced rates of movement, indicating a functional defect. These results demonstrate that C. elegans muscle development is altered in response to spaceflight. This altered development occurs at the level of gene transcription and was observed in the presence of innervation, not simply in isolated cells. This important finding coupled with past observations of decreased levels of the same ...
The nematode worm Caenorhabditis elegans is a model system for the study of the genetic basis of aging. Maternal-effect mutations in four genes-clk-1, clk-2, clk-3, and gro-1- interact genetically to determine both the duration of development and life-span. Analysis of the phenotypes of these mutants suggests the existence of a general physiological clock in the worm. Mutations in certain genes involved in dauer formation (an alternative larval stage induced by adverse conditions in which development is arrested) can also extend life-span, but the life extension of Clock mutants appears to be independent of these genes. The daf-2(e1370) clk-1(e2519) worms, which carry life-span-extending mutations from two different pathways, live nearly five times as long as wild-type worms.. ...
We describe a general strategy for the genetic mapping in parallel of multiple restriction fragment length polymorphism (RFLP) loci. This approach allows the systematic identification for cloning of physical genetic loci within about 100 kb of any gene in Caenorhabditis elegans. We have used this strategy of parallel RFLP mapping to clone the heterochronic gene lin-14, which controls the timing and sequence of many C. elegans postembryonic developmental events. We found that of about 400 polymorphic loci in the C. elegans genome associated with the Tc1 family of repetitive elements, six are within 0.3 map unit of lin-14. The three closest lin-14-linked Tc1-containing restriction fragments were cloned and used to identify by hybridization an 830-kb region of contiguous cloned DNA fragments assembled from cosmid and yeast artificial chromosome libraries. A lin-14 intragenic recombinant that separated a previously cryptic lin-14 semidominant mutation from a cis-acting lin-14 suppressor mutation was ...
The germ cells of multicellular organisms protect their developmental potential through specialized mechanisms. A shared feature of germ cells from worms to humans is the presence of nonmembrane-bound, ribonucleoprotein organelles called germ granules. Depletion of germ granules in Caenorhabditis elegans (i.e., P granules) leads to sterility and, in some germlines, expression of the neuronal transgene unc-119::gfp and the muscle myosin MYO-3. Thus, P granules are hypothesized to maintain germ cell totipotency by preventing somatic development, although the mechanism by which P granules carry out this function is unknown. In this study, we performed transcriptome and single molecule RNA-FISH analyses of dissected P granule-depleted gonads at different developmental stages. Our results demonstrate that P granules are necessary for adult germ cells to downregulate spermatogenesis RNAs and to prevent the accumulation of numerous soma-specific RNAs. P granule-depleted gonads that express the ...
TY - JOUR. T1 - The human GRB2 and Drosophila Drk genes can functionally replace the Caenorhabditis elegans cell signaling gene sem-5. AU - Stern, M. J.. AU - Marengere, L. E.M.. AU - Daly, R. J.. AU - Lowenstein, E. J.. AU - Kokel, M.. AU - Batzer, A.. AU - Olivier, P.. AU - Pawson, T.. AU - Schlessinger, J.. PY - 1993/1/1. Y1 - 1993/1/1. N2 - Mutations in the Caenorhabditis elegans gene sem-5 affect cell signaling processes involved in guiding a class of cell migrations and inducing vulval cell fates. The sem-5 sequence encodes a protein comprised almost exclusively of SH2 and SH3 domains (SH, src homology region) that are found together in many signaling proteins and nonreceptor tyrosine kinases. A human protein, GRB2, was identified by its ability to associate with the activated human epidermal growth factor receptor (hEGFR). The GRB2 and Sem-5 proteins share an identical architecture of their SH2 and SH3 domains and 58% amino acid sequence identity. Here we demonstrate that GRB2 and a ...
TY - JOUR. T1 - The Caenorhabditis elegans AMP-activated protein kinase AAK-2 is phosphorylated by LKB1 and is required for resistance to oxidative stress and for normal motility and foraging behavior. AU - Lee, Hyojin. AU - Jeong, Soo Cho. AU - Lambacher, Nils. AU - Lee, Jieun. AU - Lee, Se Jin. AU - Tae, Hoon Lee. AU - Gartner, Anton. AU - Koo, Hyeon Sook. PY - 2008/5/30. Y1 - 2008/5/30. N2 - AAK-2 is one of two α isoforms of the AMP-activated protein kinase in Caenorhabditis elegans and is involved in life span maintenance, stress responses, and germ cell cycle arrest upon dauer entry. We found that AAK-2 was phosphorylated at threonine 243 in response to paraquat treatment and that this phosphorylation depends on PAR-4, the C. elegans LKB1 homologue. Both aak-2 mutation and par-4 knockdown increased the sensitivity of C. elegans worms to paraquat, and the double deficiency did not further increase sensitivity, indicating that aak-2 and par-4 act in a linear pathway. Both mutations also ...
Brenner, S. (1974). The genetics of Caenorhabditis elegans. Genetics 77, 71-94.. Chitwood, B. G., and Chitwood, M. B. (1974). Introduction to Nematology. University Park Press, Baltimore.. Hodgkin, J. A. (1974). Genetic and Anatomical Aspects of the Caenorhabditis elegans Male, Ph.D. thesis. University of Cambridge, Cambridge, England.. Hodgkin, J. A., and Brenner, S. (1977). Mutations causing transformation of sexual phenotype in the nematode Caenorhabditis elegans. Genetics 86, 275-287.. Kimble, J., and Hirsh, D. (1979). The Postembryonic cell lineages of the hermaphrodite and male gonads in Caenorhabditis elegans. Develop. Biol. 70, 396-417.. Klass, M., Wolf, N., and Hirsh, D. (1976). Development of the male reproductive system and sexual transformation in the nematode Caenorhabditis elegans. Develop. Biol. 52, 1-18.. Seligman, I. M., Filshie, B. K., Doy, F. A., and Crossley, A. C. (1975). Hormonal control of mor-phogenetic cell death of the wing hypodermis in Lucilia cuprina. Tissue Cell ...
Defining a behavior that requires the function of specific neurons in the free-living nematode Caenorhabditis elegans can allow one to screen for mutations that disrupt the specification or function of those neurons. We identified serotonin-immunoreactive neurons required for tail curling or turnin …
Mouse mAb M38 was used in indirect immunofluorescence experiments to detect a stage-specific antigen on the surface of the first larval stage (L1) of the free-living nematode Caenorhabditis elegans, and to detect alterations in the apparent expression of this antigen in two distinct classes of C. elegans mutants. In previously described srf-2 and srf-3 mutants (Politz S. M., M. T. Philipp, M. Estevez, P.J. OBrien, and K. J. Chin. 1990. Proc. Natl. Acad. Sci. USA. 87:2901-2905), the antigen is not detected on the surface of any stage. Conversely, in srf-(yj43) and other similar mutants, the antigen is expressed on the surface of the first through the fourth (L4) larval stages. To understand the molecular basis of these alterations, the antigen was characterized in gel immunoblotting experiments. After SDS-PAGE separation and transfer to nitrocellulose, M38 detected a protein antigen in extracts of wild-type L1 populations. The antigen was sensitive to digestion by Pronase and O-glycanase ...
The detection and abundance of Escherichia coli in water is used to monitor and mandate the quality of drinking and recreational water. Distinguishing commensal waterborne E. coli isolates from those that cause diarrhea or extraintestinal disease in humans is important for quantifying human health risk. A DNA microarray was used to evaluate the distribution of virulence genes in 148 E. coli environmental isolates from a watershed in eastern Ontario, Canada, and in eight clinical isolates. Their pathogenic potential was evaluated with Caenorhabditis elegans, and the concordance between the bioassay result and the pathotype deduced by genotyping was explored. Isolates identified as potentially pathogenic on the basis of their complement of virulence genes were significantly more likely to be pathogenic to C. elegans than those determined to be potentially nonpathogenic. A number of isolates that were identified as nonpathogenic on the basis of genotyping were pathogenic in the infection assay, ...
Genetic and embryological experiments have established the Caenorhabditis elegans adult hermaphrodite gonad as a paradigm for studying the control of germline development and the role of soma-germline interactions. We describe ultrastructural features relating to essential germline events and the so …
P-glycoproteins can cause multidrug resistance in mammalian tumor cells by active extrusion of cytotoxic drugs. The natural function of these evolutionarily conserved, membrane-bound ATP binding transport proteins is unknown. In mammals, P-glycoproteins are abundantly present in organs associated with the digestive tract. We have studied the tissue-specific expression of Caenorhabditis elegans P-glycoprotein genes pgp-1 and pgp-3 by transformation of nematodes with pgp-lacZ gene fusion constructs in which the promoter area of the pgp genes was fused to the coding region of lacZ. Expression of pgp-1 and pgp-3, as inferred from pgp-lacZ transgenic nematodes, was confined to the intestinal cells. The expression patterns of both genes were virtually indistinguishable. Quantitative analysis of pgp mRNA levels during development showed that pgp-1, -2, and -3 were expressed throughout the life cycle of C.elegans, albeit with some variation indicating developmental regulation. The expression of P-glycoprotein
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.. ...
Aging is characterized by general physiological decline over time. A hallmark of human senescence is the onset of various age-related afflictions including neurodegeneration, cardiovascular disease and cancer. Although environmental and stochastic factors undoubtedly contribute to the increased incidence of disease with age, recent studies suggest that intrinsic genetic determinants govern both life span and overall health. Current aging research aims at achieving the longevity dividend, in which life span extension in humans is accomplished with a concomitant increase in the quality of life (Olshansky et al., 2007). Significant progress has been made using model organisms, especially the nematode worm Caenorhabditis elegans, to delineate the genetic and biochemical pathways involved in aging to identify strategies for therapeutic intervention in humans. In this review, we discuss how C. elegans has contributed to our understanding of insulin signaling and aging. ...
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As a consequence of the Earths axial rotation, organisms display daily recurring rhythms in behavior and biochemical properties, such as hormone titers. The neuronal system controlling such changes is best studied in the fruit fly Drosophila melanogaster. In the nematode worm Caenorhabditis elegans, most homologs of these genes function in the heterochronic pathway controlling the (timing of) developmental events. Recent data indicate that in the worm at least one of the genes involved in developmental timing is also active in circadian rhythm control, thereby opening up new perspectives on a central (neuronal) timer interfering with many processes. Also, new neuropeptidergic clock homologs have been identified in nematodes, supporting the idea of a broad range of clock-regulated targets. We will describe the current knowledge on homologous clock genes in C. elegans with a focus on the recently discovered pigment dispersing factor gene homologs. Similarities between developmental and daily ...
The pace of technical developments allowing the direct manipulation of genome sequences has seen a marked acceleration in recent years with the emergence of RNA-targeted nucleases derived from bacterial immune systems (Doudna and Charpentier 2014; Zetsche et al. 2015). In particular, the binary system relying on the Streptococcus pyogenes Cas9 endonuclease targeted by CRISPR (clustered, regularly interspaced, short, palindromic repeat) RNAs has been successfully used to generate point mutations, deletion, or DNA insertions in an ever-growing number of experimental systems. S. pyogenes CRISPR/Cas9 has been adapted early on in the model nematode Caenorhabditis elegans (Friedland et al. 2013; Dickinson et al. 2013; Chen et al. 2013; Frøkjær-Jensen 2013; Dickinson and Goldstein 2016). Previously, heritable genome engineering could only be achieved in C. elegans by remobilizing a Drosophila Mos1 transposon, which could be inserted and excised in the germline (Robert and Bessereau 2007; ...
The vaccinia-related kinases (VRKs) are highly conserved throughout the animal kingdom and phosphorylate several chromatin proteins and transcription factors. In early Caenorhabditis elegans embryos, VRK-1 is required for proper nuclear envelope formation. In this work, we present the first investigation of the developmental role of VRKs by means of a novel C. elegans vrk-1 mutant allele. We found that VRK-1 is essential in hermaphrodites for formation of the vulva, uterus, and utse and for development and maintenance of the somatic gonad and thus the germ line. VRK-1 regulates anchor cell polarity and the timing of anchor cell invasion through the basement membranes separating vulval and somatic gonadal cells during the L3 larval stage. VRK-1 is also required for proper specification and proliferation of uterine cells and sex myoblasts. Expression of the fibroblast growth factor-like protein EGL-17 and its receptor EGL-15 is reduced in vrk-1 mutants, suggesting that VRK-1 might act at least ...
Mutations in the gene unc-53 of Caenorhabditis elegans result in behavioral and anatomical abnormalities. Immunocytochemistry and electron microscopy revealed neuroanatomical defects in all main longitudinal nervous tracts. Whole tracts were found to
Large-conductance calcium and voltage-activated potassium channels, termed SLO-1 (or BK), are pivotal players in the regulation of cell excitability across the animal phyla. Furthermore, emerging evidence indicates that these channels are key mediators of a number of neuroactive drugs, including the most recent new anthelmintic, the cyclo-octadepsipeptide emodepside. Detailed reviews of the structure, function and pharmacology of BK channels have recently been provided (Salkoff et al. in Nat Rev Neurosci 7:921-931, 2006; Ghatta et al. in Pharmacol Ther 110:103-116, 2006) and therefore these aspects will only briefly be covered here. The purpose of this review is to discuss how SLO-1 channels might function as regulators of neural transmission and network activity. In particular, we focus on the role of SLO-1 in the regulation of Caenorhabditis elegans behaviour and highlight the role of this channel as an effector for pleiotropic actions of neuroactive drugs, including emodepside. On the premise ...
Microsporidia comprise a phylum of obligate intracellular pathogens related to fungi that infect virtually all animals. Recently, the nematode Caenorhabditis elegans has been developed as a convenient model for studying microsporidia infection in a whole-animal host through the identification and characterization of a natural microsporidian pathogen of this commonly studied laboratory organism. The C. elegans natural microsporidian pathogen is named Nematocida parisii, and it causes a lethal intestinal infection in C. elegans. Comparison of the genomes of N. parisii and its closely related species Nematocida sp. 1, together with the genomes of other microsporidian species, has provided insight into the evolutionary events that led to the emergence of the large, specialized microsporidia phylum. Cell biology studies of N. parisii infection in C. elegans have shown how N. parisii restructures host intestinal cells and, in particular, how it hijacks host exocytosis for nonlytic exit to facilitate
Abstract The insulin/insulin-like growth factor-like signaling (IIS) pathway in metazoans has evolutionarily conserved roles in growth control, metabolic homeostasis, stress responses, reproduction, and lifespan. Genetic manipulations that reduce IIS in the nematode worm Caenorhabditis elegans, the fruit fly Drosophila melanogaster, and the mouse have been shown not only to produce substantial increases in lifespan but also to ameliorate several age-related diseases. In C. elegans, the multitude of phenotypes produced by the reduction in IIS are all suppressed in the absence of the worm FOXO transcription factor, DAF-16, suggesting that they are all under common regulation. It is not yet clear in other animal models whether the activity of FOXOs mediate all of the physiological effects of reduced IIS, especially increased lifespan. We have addressed this issue by examining the effects of reduced IIS in the absence of dFOXO in Drosophila, using a newly generated null allele of dfoxo. We found ...
Extensive studies have been carried out on Caenorhabditis elegans as a model organism to elucidate mechanisms of aging and the effects of perturbing known aging-related genes on lifespan and behavior. This research has generated large amounts of experimental data that is increasingly difficult to integrate and analyze with existing databases and domain knowledge. To address this challenge, we demonstrate a scalable and effective approach for automatic evidence gathering and evaluation that leverages existing experimental data and literature-curated facts to identify genes involved in aging and lifespan regulation in C. elegans. We developed a semantic knowledge base for aging by integrating data about C. elegans genes from WormBase with data about 2005 human and model organism genes from GenAge and 149 genes from GenDR, and with the Bio2RDF network of linked data for the life sciences. Using HyQue (a Semantic Web tool for hypothesis-based querying and evaluation) to interrogate this knowledge base, we
RNA interference (RNAi) is a widespread and widely exploited phenomenon which has potential as a strategy for both the treatment of disease and pest control. RNAi results in down‐regulation of a specific gene in response to the production of small interfering RNAs (siRNAs). RNAi is one of a family of processes mediated by small non‐coding RNAs [1], [2]. In Caenorhabditis elegans, and in a number of other organisms, RNAi is systemic so that the introduction of dsRNA into one tissue triggers gene silencing in other tissues [3], [4], [5], [6], [7]. Furthermore, systemic RNAi enables C. elegans and other organisms to exhibit environmental RNAi [5]. For example, feeding C. elegans on bacteria expressing dsRNA initiates a widespread RNAi response [8], [9]. Studies in C. elegans and other organisms have provided mechanistic insights into RNAi [4], [10], [11], [12], [13], although the role of exogenous RNAi in the normal life of C. elegans and other animals remains unclear [14].. Whilst C. elegans ...
During the course of normal embryonic and post-embryonic development, 131 cells in a Caenorhabditis elegans hermaphrodite undergo programmed cell death. Loss of function mutations in either of the genes ced-3 or ced-4 abolish cell deaths, enabling these undead cells to survive and be incorporated into the adult with no obvious deleterious consequences. Ultrastructural reconstructions have shown that undead cells exhibit many differentiated characteristics. Most of the reconstructed cells appeared to be neurons with all the characteristic features associated with such cells, such as processes, synaptic vesicles and presynaptic specializations. However, clear morphological differences were seen among the undead neurons, suggesting a diversity of cell type. One of the reconstructed cells was a rectal epithelial cell, which had displaced its lineal sister that normally functions in this role. Removal of the ability to undergo programmed cell death by mutation therefore reveals a diversity of ...
We are studying the development of the intestine in the small free-living nematode worm Caenorhabditis elegans. The worm intestine develops as a simple clone of cells, entirely deriving from a single cell in the eight-cell embryo. We mainly focus on the transcription factor network that drives development of the intestine. From our work and that of others, we now know all the core transcription factors that control intestinal genes, from specification to differentiation, and they all are GATA factors similar to the factors that are central to the development of the human intestine. We are now trying to figure out how these factors actually work, i.e. to define the molecular and thermodynamic basis of developmental specificity. Does all the specificity reside in the DNA binding domain? And if so, how much does the binding free energy to an intestinal gene differ from the binding free energy to a gene expressed in a different lineage, e.g. the hypodermis (skin)? Are there other protein domains ...
During gastrulation of the nematode worm Caenorhabditis elegans, individual cells ingress into a solid ball of cells. Gastrulation in a basal nematode, in contrast, has now been found to occur by invagination into a blastocoel, revealing an unanticipated embryological affinity between nematodes and all other triploblastic metazoans. ...
LAG1 is a longevity gene, the first such gene to be identified and cloned from the yeast Saccharomyces cerevisiae. A close homolog of this gene, which we call LAC1, has been found in the yeast genome. We have cloned the human homolog of LAG1 with the ultimate goal of examining its possible function in human aging. In the process, we have also cloned a homolog from the nematode worm Caenorhabditis elegans. Both of these homologs, LAG1Hs and LAG1Ce-1, functionally complemented the lethality of a lag1delta lac1delta double deletion, despite low overall sequence similarity to the yeast proteins. The proteins shared a short sequence, the Lag1 motif, and a similar transmembrane domain profile. Another, more distant human homolog, TRAM, which lacks this motif, did not complement. LAG1Hs also restored the life span of the double deletion, demonstrating that it functions in establishing the longevity phenotype in yeast. LAG1Hs mapped to 19p12, and it was expressed in only three tissues: brain, skeletal ...
Caenorhabditis elegans MIG-13 protein: required for positioning of Q neuroblasts and their descendents along the anteroposterior axis; isolated from Caenorhabditis elegans; amino acid sequence in first source; GenBAnk AF150958
For the first days, we will introduce students to the nematode C. elegans. Students will work with different experimental set-ups that will allow us to explore a variety of C. elegans behavior. We will analyze C. elegans behavior in response to thermal, mechanical and chemical stimuli. The transparency of the animal makes it feasible to use genetically encoded calcium sensors to monitor neural activity in response to sensory stimuli. Transgenic expression of light-activated ion channels, allows us to turn neurons on and off. These optogenetic experiments will be used to define neural requirements of sensory processing. Students will use these techniques to determine 1) how C. elegans responds and remembers the temperature at which was raised; 2) analyze the neural dynamics of a compound motor sequence that is evoked by touch; 3) determine the neural requirements of calcium channels chemosensation. These experiments are an ideal introduction to Calcium imaging optogenetics in a genetically ...
Purification of biomass ethanol from the products of brown sugar yeast-fermentation produces a large amount of residue. This fermentation residue contains abundant brown sugar-derived nutrients and is mainly used as compost or livestock feed. However, the in vivo physiological effects of oral residue ingestion are not known. The purpose of this study was to elucidate the physiological action and molecular mechanism of fermented brown sugar residue in nematode stress tolerance, aging, and lifespan using Caenorhabditis elegans. Fermented brown sugar residue was divided into two layers, supernatant and precipitate, and each was given to nematodes. Analysis of motility and survival rate under thermal stress revealed reduced mobility and increased survival rate following treatment with fermented brown sugar residue. The survival rate of nematodes under 1% H2O2 was markedly increased by the residue and mitochondrial membrane depolarization was induced and mitochondrial radical oxygen species levels increased.
Caenorhabditis elegans shares several molecular and physiological homologies with humans and thus plays a key role in studying biological processes. As a consequence, much progress has been made in automating the analysis of C. elegans. However, there is still a strong need to achieve more progress in automating the analysis of static images of adult worms. In this paper, a three-phase semi-automated system has been proposed. As a first phase, a novel segmentation framework, based on variational level sets and local pressure force function, has been introduced to handle effectively images corrupted with intensity inhomogeneity. Then, a set of robust invariant symbolic features for high-throughput screening of image-based C. elegans phenotypes are extracted. Finally, a classification model is applied to discriminate between the different subsets. The proposed system demonstrates its effectiveness in measuring morphological phenotypes in individual worms of C. elegans.. ...
Genetic studies have identified over a dozen genes that function in programmed cell death (apoptosis) in the nematode Caenorhabditis elegans(1-3). Although the ultimate effects on cell survival or engulfment of mutations in each cell death gene have been extensively described, much less is known about how these mutations affect the kinetics of death and engulfment, or the interactions between these two processes. We have used four-dimensional-Nomarski time-lapse video microscopy to follow in detail how cell death genes regulate the extent and kinetics of apoptotic cell death and removal in the early C. elegans embryo. Here we show that blocking engulfment enhances cell survival when cells are subjected to weak pro-apoptotic signals. Thus, genes that mediate corpse removal can also function to actively kill cells.. ...
A specific behavioural response of Caenorhabditis elegans, the rapid increase of locomotion in response to anoxia/reoxygenation called the O2-ON response, has been used to model key aspects of ischaemia/reperfusion injury. A genetic suppressor screen demonstrated a direct causal role of CYP (cytochrome P450)-13A12 in this response and suggested that CYP-eicosanoids, which in mammals influence the contractility of cardiomyocytes and vascular smooth muscle cells, might function in C. elegans as specific regulators of the body muscle cell activity. In the present study we show that co-expression of CYP-13A12 with the NADPH-CYP-reductase EMB-8 in insect cells resulted in the reconstitution of an active microsomal mono-oxygenase system that metabolized EPA (eicosapentaenoic acid) and also AA (arachidonic acid) to specific sets of regioisomeric epoxy and hydroxy derivatives. The main products included 17,18-EEQ (17,18-epoxyeicosatetraenoic acid) from EPA and 14,15-EET (14,15-epoxyeicosatrienoic acid) ...
Benzimidazole anti-microtubule drugs, such as benomyl, induce paralysis and slow the growth of the nematode Caenorhabditis elegans. We have identified 28 mutations in C. elegans that confer resistance to benzimidazoles. All resistant mutations map to a single locus, ben-1. Virtually all these mutations are genetically dominant. Molecular cloning and DNA sequence analysis established that ben-1 encodes a beta-tubulin. Some resistant mutants are completely deleted for the ben-1 gene. Since the deletion strains appear to be fully resistant to the drugs, the ben-1 product appears to be the only benzimidazole-sensitive beta-tubulin in C. elegans. Furthermore, since animals lacking ben-1 are viable and coordinated, the ben-1 beta-tubulin appears to be nonessential for growth and movement. The ben-1 function is likely to be redundant in the nematode genome. ...
Approximately 10% of Caenorhabditis elegans nervous system synapses are electrical, that is, gap junctions composed of innexins. The locomotory nervous system consists of several pairs of interneurons and three major classes of motor neurons, all with stereotypical patterns of connectivity that include gap junctions. Mutations in the two innexin genes unc-7 and unc-9 result in identical uncoordinated movement phenotypes, and their respective gene products were investigated for their contribution to electrical synapse connectivity. unc-7 encodes three innexin isoforms. Two of these, UNC-7S and UNC-7SR, are functionally equivalent and play an essential role in coordinated locomotion. UNC-7S and UNC-7SR are widely expressed and co-localize extensively with green fluorescent protein-tagged innexin UNC-9 in the ventral and dorsal nerve cords. A subset of UNC-7S/SR expression visualizes gap junctions formed between the AVB forward command interneurons and their B class motor neuron partners. Experiments
Many crucial events in metazoan development and physiology are governed by diffusible signals that trigger specific responses in highly restricted subsets of cells. This exquisite specificity of intercellular signaling requires precisely controlled expression of receptors and downstream signaling components that effect appropriate responses. The nematode Caenorhabditis elegans has proven a valuable model for the study of signaling specificity, notably for mechanisms of signaling through the Epidermal growth factor (EGF) receptor (for a review, see Moghal and Sternberg, 2003). The sole EGF-like ligand and EGF receptor in the C. elegans genome are encoded by the genes lin-3 and let-23, respectively (Hill and Sternberg, 1992; Aroian et al., 1990) (Wormbase WS210). Recently we described a role for LET-23 in the regulation of C. elegans behavior (Van Buskirk and Sternberg, 2007). Caenorhabditis elegans develops through four larval stages before adulthood, and each larval molt is preceded by ...
TY - JOUR. T1 - Caenorhabditis elegans cDNA for a Menkes/Wilson disease gene homologue and its function in a yeast CCC2 gene deletion mutant. AU - Sambongi, Yoshihiro. AU - Wakabayashi, Tokumitsu. AU - Yoshimizu, Takao. AU - Omote, Hiroshi. AU - Oka, Toshihiko. AU - Futai, Masamitsu. PY - 1997/6. Y1 - 1997/6. N2 - The full-length cDNA coding for a putative copper transporting P-type ATPase (Cu2+-ATPase) was cloned from Caenorhabditis elegans. The putative Cu2+-ATPase is a 1,238-amino acid protein, and highly homologous to the Menkes and Wilson disease gene products mutations of which are responsible for human defects of copper metabolism. The Saccharomyces cerevisiae mutant with a disrupted CCC2 gene (yeast Menkes/Wilson disease gene homologue) was rescued by the cDNA for the C. elegans Cu2+-ATPase but not by the cDNA with an Asp-786 (an invariant phosphorylation site) to Asn mutation, suggesting that the C. elegans Cu2+-ATPase functions as a copper transporter in yeast. The expressed C. elegans ...
Mutations in the human Mid1 gene cause Opitz G/BBB syndrome, which is characterized by various midline closure defects. The Caenorhabditis elegans homolog of Mid1, madd-2, positively regulates signaling by the unc-40 Netrin receptor during the extension of muscle arms to the midline and in axon guidance and branching. During uterine development, a specialized cell called anchor cell (AC) breaches the basal laminae separating the uterus from the epidermis and invades the underlying vulval tissue. AC invasion is guided by an UNC-6 Netrin signal from the ventral nerve cord and an unknown guidance signal from the vulval cells. Using genetic epistasis analysis, we show that madd-2 regulates AC invasion downstream of or in parallel with the Netrin signaling pathway. Measurements of AC shape, polarity and dynamics indicate that MADD-2 prevents the formation of ectopic AC protrusions in the absence of guidance signals. We propose that MADD-2 represses the intrinsic invasive capacity of the AC, while the ...
The Caenorhabditis elegans genome is known to code for at least 1149 G protein-coupled receptors (GPCRs), but the GPCR(s) critical to the regulation of reproduction in this nematode are not yet known. This study examined whether GPCRs orthologous to human gonadotropin-releasing hormone receptor (GnRHR) exist in C. elegans. Our sequence analyses indicated the presence of two proteins in C. elegans, one of 401 amino acids [GenBank: NP_491453; WormBase: F54D7.3] and another of 379 amino acids [GenBank: NP_506566; WormBase: C15H11.2] with 46.9% and 44.7% nucleotide similarity to human GnRHR1 and GnRHR2, respectively. Like human GnRHR1, structural analysis of the C. elegans GnRHR1 orthologue (Ce-GnRHR) predicted a rhodopsin family member with 7 transmembrane domains, G protein coupling sites and phosphorylation sites for protein kinase C. Of the functionally important amino acids in human GnRHR1, 56% were conserved in the C. elegans orthologue. Ce-GnRHR was actively transcribed in adult worms and
Both dauer formation (a stage of developmental arrest) and adult life-span in Caenorhabditis elegans are negatively regulated by insulin-like signaling, but little is known about cellular pathways that mediate these processes. Autophagy, through the sequestration and delivery of cargo to the lysosomes, is the major route for degrading long-lived proteins and cytoplasmic organelles in eukaryotic cells. Using nematodes with a loss-of-function mutation in the insulin-like signaling pathway, we show that bec-1, the C. elegans ortholog of the yeast and mammalian autophagy gene APG6/VPS30/beclin1, is essential for normal dauer morphogenesis and life-span extension. Dauer formation is associated with increased autophagy and also requires C. elegans orthologs of the yeast autophagy genes APG1, APG7, APG8, and AUT10. Thus, autophagy is a cellular pathway essential for dauer development and life-span extension in C. elegans.. ...
TY - JOUR. T1 - Origin, properties, and regulated expression of multiple mRNAs encoded by the protein kinase C1 gene of Caenorhabditis elegans. AU - Land, Marianne. AU - Islas-Trejo, Alma. AU - Rubin, Charles S.. N1 - Copyright: Copyright 2005 Elsevier B.V., All rights reserved.. PY - 1994/5/20. Y1 - 1994/5/20. N2 - Recently, we cloned and characterized cDNA encoding a novel, protein kinase C (designated PKC1B) from Caenorhabditis elegans. PKC1B (707 amino acid residues) is a developmentally regulated, calcium-independent kinase that is expressed exclusively in sensory neurons and related interneurons. We have now discovered a mechanism by which a second, distinct mRNA (PKC1A mRNA) with increased protein coding potential is generated from the C. elegans PKC1 gene. PKC1A mRNA is produced in a process that involves the utilization of an alternative, distal promoter, the incorporation of two unique exons into the mRNA, and alternative cis/trans splicing. Diversity among PKC1 gene transcripts is ...
In nematodes an alternative third larval stage, often called the dauer stage, allows the animals to weather periods of low food availability (if free living) or to disperse (if parasitic). Recently, studies of mutations in the nematode Caenorhabditis elegans have indicated that mutations in age-1 and daf-2 , genes that control the entry into and exit from the dauer stage, have a profound effect upon the life span of the animal. Catalase activity is increased in age-1 and daf-2 animals and might be important for life-span extension. We show that C. elegans contains two catalases, CTL-2 is a typical animal peroxisomal catalase. The ctl-1 gene encodes the first cytosolic catalase identified in an animal. The ctl-1 catalase is regulated by age-1 and daf-2 and is responsible for the increase in catalase activity seen in these mutants. We have identified a mutation affecting the expression of ctl-1. The ctl-1 mutation causes the early death of dauer larvae and prevents the life-span extension of the ...
The prototype of the Cdx family of homeodomain transcription factors is the Drosophila caudal protein. The initial maternal expression of caudal mRNA is ubiquitous and a posterior to anterior gradient of the protein develops during the syncytial blastoderm stage and persists until the onset of cellularization. Zygotic expression, which commences in the cellular blastoderm stage, is also localized to the posterior in a region which gives rise to terminal abdominal structures and the hindgut. During later embryonic development, expression of caudal is found in the midgut, hindgut and Malpigian tubules (MacDonald and Struhl, 1986; Mlodzik and Gehring, 1987).. Caudal homologues have been identified in a wide range of animal groups. A caudal‐related gene with a similar posterior expression pattern has been cloned from the short or intermediate germ band insect Bombyx mori and homologues are present in other invertebrates, including the nematode worm Caenorhabditis elegans and the annelid worm ...
Howard Robert Horvitz (born May 8, 1947) is an American biologist best known for his research on the nematode worm Caenorhabditis elegans, for which he was awarded the 2002 Nobel Prize in Physiology or Medicine, together with Sydney Brenner and John E. Sulston. Horvitz was born in Chicago, Illinois to Jewish parents, the son of Mary R. (Savit), a school teacher, and Oscar Freedom Horvitz, a GAO accountant. He majored in mathematics at Massachusetts Institute of Technology, where he joined Alpha Epsilon Pi and spent his summers working for IBM, at first wiring panels for accounting machines and then in his final summer helping to develop IBMs Conversational Programming System. During his senior year, Horvitz took his first courses in biology and was encouraged by his professors to continue to study biology in graduate school, despite his limited coursework in the field. After he completed his undergraduate studies in 1968, he enrolled in graduate studies in biology at Harvard University, where ...
The role of lipids in the process of embryonic development of Caenorhabditis elegans is still poorly understood. Cytochrome P450s, a class of lipid-modifying enzymes, are good candidates to be involved in the production or degradation of lipids essential for development. We investigated two highly similar cytochrome P450s in C. elegans, cyp-31A2 and cyp-31A3, that are homologs of the gene responsible for Bietti crystalline corneoretinal dystrophy in humans. Depletion of both cytochromes either by RNAi or using a double deletion mutant, led to the failure of establishing the correct polarity of the embryo and to complete the extrusion of the polar bodies during meiosis. In addition, the egg became osmotic sensitive and permeable to dyes. The phenotype of cyp-31A2 or cyp-31A3 is very similar to a class of mutants that have polarization and osmotic defects (POD), thus the genes were renamed to pod-7 and pod-8, respectively. Electron microscopic analysis demonstrated that the activity of pod-7/pod-8 ...
Aims: To investigate the role of endogenous hydrogen sulfide (H2S) in the control of aging and healthspan of Caenorhabditis elegans. Results: We show that the model organism, C. elegans, synthesizes H2S. Three H2S-synthesizing enzymes are present in C. elegans, namely cystathionine γ lyase (CSE), cystathionine β synthetase, and 3-mercaptopyruvate transferase (MPST or 3-MST). Genetic deficiency of mpst-1 (3-MST orthologue 1), but not cth-2 (CSE orthologue), reduced the lifespan of C. elegans. This effect was reversed by a pharmacological H2S donor (GYY4137). GYY4137 also reduced detrimental age-dependent changes in a range of physiological indices, including pharyngeal contraction and defecation. Treatment of C. elegans with GYY4137 increased the expression of several age-related, stress response, and antioxidant genes, whereas MitoSOX Red fluorescence, indicative of reactive oxygen species generation, was increased in mpst-1 knockouts and decreased by GYY4137 treatment. GYY4137 additionally ...
The Caenorhabditis elegans run gene encodes a Runt domain factor. Runx1, Runx2, and Runx3 are the three known mammalian homologs of run. Runx1, which plays an essential role in hematopoiesis, has been identified at the breakpoint of chromosome translocations that are responsible for human leukemia. Runx2 plays an essential role in osteogenesis, and inactivation of one allele of Runx2 is responsible for the human disease cleidocranial dysplasia. To understand the role of run in C. elegans, we used transgenic run::GFP reporter constructs and a double-stranded RNA-mediated interference method. The expression of run was detected as early as the bean stage exclusively in the nuclei of seam hypodermal cells and lasted until the L3 stage. At the larval stage, expression of run was additionally detected in intestinal cells. The regulatory elements responsible for the postembryonic hypodermal seam cells and intestinal cells were separately located within a 7.2-kb-long intron region. This is the first ...
Caenorhabditis elegans are free-living bacterivorous nematodes that naturally consume bacteria as food source. As an excellent genetic model, C. elegans has proven to be a successful system to study innate immune responses to human pathogens, which resulted in identification of many evolutionarily conserved defense pathways. Most of these studies examined innate immune pathway mutants in a single genetic background in response to monoculture of human pathogens that worms might not necessarily encounter in the wild. While this has led to the successful genetic dissection of these defense pathways, in order to fully understand their biological functions, the relevant ecological and evolutionary context needs to be taken into account. The bacterial environment C. elegans naturally encounter is likely to be highly heterogeneous. While many bacteria are mainly considered as dietary resource for worms, some could be potential pathogens. Worms thus constantly face the challenge to defend against the ...
Turraea fischeri is an East African traditional herb, which is widely used in traditional medicine. In this study, we profiled the secondary metabolites in the methanol extract of T. fischeri bark using HPLC-PDA-ESI-MS/MS, and 20 compounds were tentatively identified. Several isomers of the flavonolignan cinchonain-I and bis-dihydroxyphenylpropanoid-substituted catechin hexosides dominated the extract. Robust in vitro and in vivo antioxidant properties were observed in 1,1-diphenyl-2-picrylhydrazyl radical scavenging assay (DPPH) and ferric reducing antioxidant power (FRAP) assay, and in the model organism Caenorhabditis elegans. Additionally, the extract exhibited promising hepatoprotective activities in D-galactosamine (D-GaIN) treated rats. A significant reduction in the elevated levels of aspartate aminotransferase (AST), total bilirubin, gamma-glutamyltransferase (GGT), and malondialdehyde (MDA) and increase of glutathione (GSH) was observed in rats treated with the bark extract in addition to D
The nematode Caenorhabditis elegans has been much studied as a host for microbial infection. Some pathogens can infect its intestine, while others attack via its external surface. Cultures of Caenorhabditis isolated from natural environments have yielded new nematode pathogens, such as microsporidia and viruses. We report here a novel mechanism for bacterial attack on worms, discovered during investigation of a diseased and coinfected natural isolate of Caenorhabditis from Cape Verde. Two related coryneform pathogens (genus Leucobacter) were obtained from this isolate, which had complementary effects on C. elegans and related nematodes. One pathogen, Verde1, was able to cause swimming worms to stick together irreversibly by their tails, leading to the rapid formation of aggregated worm-stars. Adult worms trapped in these aggregates were immobilized and subsequently died, with concomitant growth of bacteria. Trapped larval worms were sometimes able to escape from worm-stars by undergoing autotomy,
The elt-1 RNAi phenotype provides a useful insight into the function of seam cells during postembryonic development. The loss of alae in the adult cuticle confirms the role of seam cells in producing this structure, which has previously been shown by laser ablation studies (Singh and Sulston, 1978). The apparently normal appearance of the underlying cuticle is also consistent with these previous studies and presumably this is derived from the dorsal/ventral hypodermis. RNAi of elt-1, applied during larval development, has a severe effect on the integrity of adult worms within a few hours of the L4-adult moult. Adult hermaphrodites show a `burst-vulva phenotype, in which the uterus herneates through the vulva. This is likely to be a direct consequence of seam-cell loss because the lateral seam anchors the vulval and uterine cells in position by virtue of the utse cell connection (Michaux et al., 2001; Newman et al., 2000; Sharma-Kishore et al., 1999). This hypothesis is supported by the ...
TY - JOUR. T1 - Regulation of Tcl transposable elements in Caenorhabditis elegans.. AU - Emmons, S. W.. AU - Ruan, K. S.. AU - Levitt, A.. AU - Yesner, L.. PY - 1985. Y1 - 1985. N2 - C. elegans strains contain variable numbers of a 1.6-kb transposable genetic element. Activity of this element, which is denoted Tcl, shows regulation at at least two levels. At one level, excision of Tcl elements occurs in somatic cells at a frequency several orders of magnitude higher than in germ cells. Evidence is presented suggesting that this results from regulation at the level of trans-acting functions that are required for excision or that repress excision. At the second level, germ line transposition of Tcl occurs at greater frequency in some strains than in others. The hypothesis is proposed that this is because Tcl is one component of a two-element system, the second element of which differs between strains. Evidence for a second putative transposable element family in C. elegans is presented. This ...
The Caenorhabditis elegans Regulator of Presynaptic Morphology (RPM)-1 is a member of a conserved family of proteins called Pam/Highwire/RPM-1 (PHR) proteins. PHR proteins are key regulators of neuronal development. In C. elegans, RPM-1 (regulator of presynaptic morphology-1) regulates axon termination and guidance in the mechanosensory neurons, and regulates synapse formation in the mechanosensory and motor neurons (Po et al., 2010). In adult C. elegans, RPM-1 also plays a role in axon regeneration in motor neurons (Hammarlund et al., 2009). Importantly, Drosophila Highwire, zebrafish Esrom/Phr1, and murine Phr1 also regulate synapse formation and axon extension highlighting the evolutionarily conserved function of the PHR proteins (Po et al., 2010).. Previous studies showed that RPM-1 functions, in part, as an E3 ubiquitin ligase by binding to the F box SyNaptic protein (FSN)-1 and negatively regulating a MAPK pathway that includes: the Dual Leucine zipper-bearing Kinase (DLK)-1, MAPK Kinase ...
Under experimental conditions, virtually all behaviors of Caenorhabditis elegans are achieved by combinations of simple locomotion, including forward, reversal movement, turning by deep body bending, and gradual shallow turning. To study how worms regulate these locomotion in response to sensory information, acidic pH avoidance behavior was analyzed by using worm tracking system. In the acidic pH avoidance, we characterized two types of behavioral maneuvers that have similar behavioral sequences in chemotaxis and thermotaxis. A stereotypic reversal-turn-forward sequence of reversal avoidance caused an abrupt random reorientation, and a shallow gradual turn in curve avoidance caused non-random reorientation in a less acidic direction to avoid the acidic pH. Our results suggest that these two maneuvers were each triggered by a distinct threshold pH. A simulation study using the two-distinct-threshold model reproduced the avoidance behavior of the real worm, supporting the presence of the threshold.
Neuropeptides regulate all aspects of behavior in multicellular organisms. Because of their ability to act at long distances, neuropeptides can exert their effects beyond the conventional synaptic connections, thereby adding an intricate layer of complexity to the activity of neural networks. In the nematode Caenorhabditis elegans, a large number of neuropeptide genes that are expressed throughout the nervous system have been identified.The actions of these peptides supplement the synaptic connections of the 302 neurons, allowing for fine tuning of neural networks and increasing the ways in which behaviors can be regulated. In this review, we focus on a large family of genes encoding FMRFamide-related peptides (FaRPs). These genes, the flp genes, have been used as a starting point to identifying flp genes throughout Nematoda. Nematodes have the largest family of FaRPs described thus far. The challenges in the future are the elucidation of their functions and the identification of the receptors and
Metals are major contaminants that influence human health. Many metals have physiologic roles, but excessive levels can be harmful. Advances in technology have made toxicogenomic analyses possible to characterize the effects of metal exposure on the entire genome. Much of what is known about cellular responses to metals has come from mammalian systems; however the use of non-mammalian species is gaining wider attention. Caenorhabditis elegans (C. elegans) is a small round worm whose genome has been fully sequenced and its development from egg to adult is well characterized. It is an attractive model for high throughput screens due to its short lifespan, ease of genetic mutability, low cost and high homology with humans. Research performed in C. elegans has led to insights in apoptosis, gene expression and neurodegeneration, all of which can be altered by metal exposure. Additionally, by using worms one can potentially study how the mechanisms that underline differential responses to metals in nematodes
The eukaryotic ubiquitin-conjugation system sets the turnover rate of many proteins and includes activating enzymes (E1s), conjugating enzymes (UBCs/E2s), and ubiquitin-protein ligases (E3s), which are responsible for activation, covalent attachment and substrate recognition, respectively. There are also ubiquitin-like proteins with distinct functions, which require their own E1s and E2s for attachment. We describe the results of RNA interference (RNAi) experiments on the E1s, UBC/E2s and ubiquitin-like proteins in Caenorhabditis elegans. We also present a phylogenetic analysis of UBCs. The C. elegans genome encodes 20 UBCs and three ubiquitin E2 variant proteins. RNAi shows that only four UBCs are essential for embryogenesis: LET-70 (UBC-2), a functional homolog of yeast Ubc4/5p, UBC-9, an ortholog of yeast Ubc9p, which transfers the ubiquitin-like modifier SUMO, UBC-12, an ortholog of yeast Ubc12p, which transfers the ubiquitin-like modifier Rub1/Nedd8, and UBC-14, an ortholog of Drosophila Courtless.
The nematode Caenorhabditis elegans has in recent years been proven to be a powerful in vivo model for testing antimicrobial compounds. We report here that the alkaloid compound Harmane (2-methyl-β-carboline) increases the lifespan of nematodes infected with a human pathogen, the Shiga toxin-producing Escherichia coli O157:H7 strain EDL933 and several other bacterial pathogens. This was shown to be unrelated to the weak antibiotic effect of Harmane. Using GFP-expressing E. coli EDL933, we showed that Harmane does not lower the colonization burden in the nematodes. We also found that the expression of the putative immune effector gene F35E12.5 was up-regulated in response to Harmane treatment. This indicates that Harmane stimulates the innate immune response of the nematode; thereby increasing its lifespan during bacterial infection. Expression of F35E12.5 is predominantly regulated through the p38 MAPK pathway; however, intriguingly the lifespan extension resulting from Harmane was higher in ...
An additional genetic locus in Caenorhabditis elegans, unc-116, was identified in a screen for mutations resulting in defective locomotion. unc-116 was cloned by use of a transposon insertion mutant and the physical and genetic map of the genome. The cDNA sequence predicts an 815-amino acid protein. Based upon sequence comparison and secondary structure predictions, unc-116 encodes all three domains of the kinesin heavy chain: the motor, stalk, and tail. While the motor and tail domains have a high degree of identity to the equivalent domains of cloned kinesin heavy chains, the rodII domain of the stalk is significantly shorter than those previously reported and is not predicted to form a coiled-coil alpha-helix. Analysis of mutational defects in two C. elegans genes encoding anterograde motor molecules, unc-116 and unc-104, should provide insight into the in vivo functions of these members of the kinesin heavy chain superfamily.. ...
TY - JOUR. T1 - A novel calcineurin-interacting protein, CNP-3, modulates calcineurin deficient phenotypes in Caenorhabditis elegans. AU - Kim, Yun Hee. AU - Song, Hyun Ok. AU - Ko, Kyung Min. AU - Singaravelu, Gunasekaran. AU - Jee, Chang Hoon. AU - Kang, Junsu. AU - Ahnn, Joohong. PY - 2008/6/30. Y1 - 2008/6/30. N2 - Calcineurin (Cn) is a calcium/calmodulin-dependent serine/threonine protein phosphatase that has diverse functions in different cell types and organisms. We screened proteins interacting with the C. elegans CnA homolog, TAX-6, by the yeast two-hybrid system. CNP-3 (Calcineurin interacting protein-3) is a novel protein that physically interacts with the catalytic domain of TAX-6. It is strongly expressed in the nuclei of intestine, hypodermis, dorsal uterine regions and spermatheca. Expression begins around the 60-cell stage and proceeds during all larval stages and the adult. To elucidate the biological function of cnp-3 we isolated a cnp-3 deletion mutant. Since CNP-3 binds CnA, ...
This paper presents a simple yet biologicallygrounded model for the neural control of Caenorhabditis elegans forward locomotion. We identify a minimal circuit within the C. elegans ventral cord that is likely to be sufficient to generate and sustain forward locomotion in vivo. This limited subcircuit appears to contain no obvious central pattern generated control. For that subcircuit, we present a model that relies on a chain of oscillators along the body which are driven by local and proximate mechano-sensory input. Computer simulations were used to study the model under a variety of conditions and to test whether it is behaviourally plausible. Within our model, we find that a minimal circuit of AVB interneurons and B-class motoneurons is sufficient to generate and sustain fictive forward locomotion patterns that are robust to significant environmental perturbations. The model predicts speed and amplitude modulation by the AVB command interneurons. An extended model including D-class ...
MicroRNAs (miRNAs) are small, approximately 22 nucleotide RNAs that regulate gene expression post-transcriptionally by base-pairing to complementary sites in the target mRNA. The first miRNA, lin-4, was discovered in 1993 in Caenorhabditis elegans; since then hundreds of miRNAs have been identified in C. elegans, Drosophila melanogaster, plants, mouse, and humans, where they approach a number equivalent to 1-2% of the protein-coding genes. With the exception of plants, miRNAs most commonly regulate targets by imperfectly pairing to 3 untranslated regions (UTRs), leading to translational repression or mRNA destabilization. The microRNA miR-196 is encoded at three paralogous locations in the HoxA, B, and C clusters in mammals and has conserved complementarity to the 3UTRs of Hoxb8, Hoxc8, and Hoxa7; in particular, miR-1 96 has complete complementarity to Hoxb8 with the exception of a single G:U wobble. In 2004, Yekta et al., were able to detect RNA fragments diagnostic of miR-1 96-directed ...
Despite the prominence of Caenorhabditis elegans as a major developmental and genetic model system, its phylogenetic relationship to its closest relatives has not been resolved. Resolution of these relationships is necessary for studying the steps that underlie life history, genomic, and morphological evolution of this important system. By using data from five different nuclear genes from 10 Caenorhabditis species currently in culture, we find a well resolved phylogeny that reveals three striking patterns in the evolution of this animal group: (i) Hermaphroditism has evolved independently in C. elegans and its close relative Caenorhabditis briggsae; (ii) there is a large degree of intron turnover within Caenorhabditis, and intron losses are much more frequent than intron gains; and (iii) despite the lack of marked morphological diversity, more genetic disparity is present within this one genus than has occurred within all vertebrates. ...
Progressive neuronal deterioration accompanied by sensory functions decline is typically observed during aging. On the other hand, structural or functional alterations of specific sensory neurons extend lifespan in the nematode Caenorhabditis elegans. Hormesis is a phenomenon by which the body benefits from moderate stress of various kinds which at high doses are harmful. Several studies indicate that different stressors can hormetically extend lifespan in C. elegans and suggest that hormetic effects could be exploited as a strategy to slow down aging and the development of age-associated (neuronal) diseases in humans. Mitochondria play a central role in the aging process and hormetic-like bimodal dose-response effects on C. elegans lifespan have been observed following different levels of mitochondrial stress. Here we tested the hypothesis that mitochondrial stress may hormetically extend C. elegans lifespan through subtle neuronal alterations. In support of our hypothesis we find that life-lengthening
The C. elegans hermaphrodite vulva develops during postembryonic (larval) development from ventral epidermal precursors, and connects the developing uterus to the external environment. In the adult, the vulva is necessary for egg-laying (see Egg-laying) and for copulation with males (see Male mating behavior). Vulval development has attracted general interest for three main reasons. First, it serves as a paradigm for organogenesis. In particular, vulva development represents a well-understood case in which invariant development arises from multiple cell-cell interactions. It is also a striking example of tissue remodeling: the formation of a hole at a precise location in an organism. Second, it has been important for the genetic analyses of signaling and signal transduction by epidermal growth factor (EGF)-receptor LET-23 and RAS LET-60; (see RTKRas/MAP kinase signaling), LIN-12 (see LIN-12/Notch signaling in C. elegans), and WNT (see Wnt signaling), as well as the functions of the SynMuv and ...
The C. elegans hermaphrodite vulva develops during postembryonic (larval) development from ventral epidermal precursors, and connects the developing uterus to the external environment. In the adult, the vulva is necessary for egg-laying (see Egg-laying) and for copulation with males (see Male mating behavior). Vulval development has attracted general interest for three main reasons. First, it serves as a paradigm for organogenesis. In particular, vulva development represents a well-understood case in which invariant development arises from multiple cell-cell interactions. It is also a striking example of tissue remodeling: the formation of a hole at a precise location in an organism. Second, it has been important for the genetic analyses of signaling and signal transduction by epidermal growth factor (EGF)-receptor LET-23 and RAS LET-60; (see RTKRas/MAP kinase signaling), LIN-12 (see LIN-12/Notch signaling in C. elegans), and WNT (see Wnt signaling), as well as the functions of the SynMuv and ...
TY - JOUR. T1 - Caenorhabditis elegans as an environmental monitor using DNA microarray analysis. AU - Custodia, N.. AU - Won, S. J.. AU - Novillo, A.. AU - Wieland, M.. AU - Li, C.. AU - Callard, I. P.. N1 - Copyright: Copyright 2020 Elsevier B.V., All rights reserved.. PY - 2001. Y1 - 2001. N2 - In order to assist in the identification of possible endocrine disrupting chemicals (EDC) in groundwater, we are developing Caenorhabolitis elegans as a high throughput bioassay system in which responses to EDC may be detected by gene expression using DNA microarray analysis. As a first step we examined gene expression patterns and vitellogenin responses of this organism to vertebrate steroids, in liquid culture. Western blotting showed the expected number and size of vitellogenin translation products after estrogen exposure. At 10-9 M, vitellogenin decreased, but at 10-7 and 10-5, vitellogenin was increased. Testosterone (10-5 M) increased the synthesis of vitellogenin, but progesterone-treated ...
Multiphoton laser scanning microscopy (MPLSM) enables the production of long timelapse recordings from live fluorescent specimens. 1047- and 900-nm excitation were used to image both a vital fluorescent membrane probe, FM 4-64, and a modified green fluorescent protein (GFP) in live Caenorhabditis elegans embryos. Automated four-dimensional (4D) data collection yielded individual recordings comprising thousands of images, each allowing analysis of all of the cell divisions, contacts, migrations, and fusions that occur during a span of several hours of embryogenesis.. ©1998 Optical Society of America. Full Article , PDF Article ...
Current Name: Aphyosemion elegans. Describer(s), Year: (Boulenger, 1899). IDENTITY: elegans A.. Family-group Names: Nothobranchiidae Garman, 1895 , Nothobranchiinae Garman, 1895 , Nothobranchiini Garman, 1895 , Aphyosemina Huber, 2000 (#Aphyosemiina #Aphyosemionina) Genus: Aphyosemion Myers, 1924. Subgenus: Aphyosemion Myers, 1924. Abbreviated genus: A.. Abbreviated subgenus: (A.). Species: elegans. Index name: elegans: Aphyosemion elegans. Full name: Aphyosemion (Aphyosemion) elegans. TYPOLOGY: elegans A.. Original name: Haplochilus elegans. Describer(s): Boulenger. Year of description: 1899. Original description: Boulenger, G.A. 1899. Poissons nouveaux du Congo. Cinquième Partie. Cyprins, Silures, Cyprinodontes, Acanthopterygiens. Ann. Mus. Congo Belge, Tervuren, Zool. Ser., 1 (5): 113, pl. 47 (fig. 2).. Gender/Accordance: [Subst.]. SYSTEMATICS: elegans A.. Current status: valid sp.. Status evaluation (current): discussed {no red bars on male sides are mentioned in the description, only -red- ...
0, Molecular and genetic characterization of GON-2, a TRPM cation channel required for gonadogenesis in Caenorhabditis elegans A Thesis Submitted to the Faculty in partial fulfillment of the requirements for the degree of o Doctor of Philosophy in Biological Sciences by Rachel West DARTMOUTH COLLEGE Hanover, New Hampshire January, 2004 Examining9ommittee: Eric }. IAInbig (Chair) c:, Victor R. A)fibros Eleanor M. Maine Carol L. Folt Dean of Graduate Studies ...
Phosphine is a fumigant used to protect stored commodities from infestation by pest insects, though high-level phosphine resistance in many insect species threatens the continued use of the fumigant. The mechanisms of toxicity and resistance are not clearly understood. In this study, the model organism, Caenorhabditis elegans, was employed to investigate the effects of phosphine on its proposed in vivo target, the mitochondrion. We found that phosphine rapidly perturbs mitochondrial morphology, inhibits oxidative respiration by 70%, and causes a severe drop in mitochondrial membrane potential ({Delta}{Psi}m) within 5 h of exposure. We then examined the phosphine-resistant strain of nematode, pre-33, to determine whether resistance was associated with any changes to mitochondrial physiology. Oxygen consumption was reduced by 70% in these mutant animals, which also had more mitochondrial genome copies than wild-type animals, a common response to reduced metabolic capacity. The mutant also had an ...
We have examined the cortex of Caenorhabditis elegans eggs during pseudocleavage (PC), a period of the first cell cycle which is important for the generation of asymmetry at first cleavage (Strome, S. 1989. Int. Rev. Cytol. 114: 81-123). We have found that directed, actin dependent, cytoplasmic, and cortical flow occurs during this period coincident with a rearrangement of the cortical actin cytoskeleton (Strome, S. 1986. J. Cell Biol. 103: 2241-2252). The flow velocity (4-7 microns/min) is similar to previously determined particle movements driven by cortical actin flows in motile cells. We show that directed flows occur in one of the daughters of the first division that itself divides asymmetrically, but not in its sister that divides symmetrically. The cortical and cytoplasmic events of PC can be mimicked in other cells during cytokinesis by displacing the mitotic apparatus with the microtubule polymerization inhibitor nocodazole. In all cases, the polarity of the resulting cortical and ...
Glutathione is the most abundant thiol in the vast majority of organisms and is maintained in its reduced form by the flavoenzyme glutathione reductase. In this work, we describe the genetic and functional analysis of the Caenorhabditis elegans gsr-1 gene that encodes the only glutathione reductase protein in this model organism. By using green fluorescent protein reporters we demonstrate that gsr-1 produces two GSR-1 isoforms, one located in the cytoplasm and one in the mitochondria. gsr-1 loss of function mutants display a fully penetrant embryonic lethal phenotype characterized by a progressive and robust cell division delay accompanied by an aberrant distribution of interphasic chromatin in the periphery of the cell nucleus. Maternally expressed GSR-1 is sufficient to support embryonic development but these animals are short-lived, sensitized to chemical stress and have increased mitochondrial fragmentation and lower mitochondrial DNA content. Furthermore, the embryonic lethality of gsr-1 ...
The protease separase plays a key role in sister chromatid disjunction and centriole disengagement. To maintain genomic stability, separase activity is strictly regulated by binding of an inhibitory protein, securin. Despite its central role in cell division, the separase and securin complex is poorly understood at the structural level. This is partly owing to the difficulty of generating a sufficient quantity of homogeneous, stable protein. Here, we report the production of Caenorhabditis elegans separase-securin complex, and its characterization using biochemical methods and by negative staining electron microscopy. Single particle analysis generated a density map at a resolution of 21-24 Å that reveals a close, globular structure of complex connectivity harbouring two lobes. One lobe matches closely a homology model of the N-terminal HEAT repeat domain of separase, whereas the second lobe readily accommodates homology models of the separase C-terminal death and caspase-like domains. The ...
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