Sulston JE et al. (1992) Nature "The C. elegans genome sequencing project: a beginning."

Wilson RK, Metzstein MM, Ainscough R, Waterston RH, Coulson AR, Craxton M, Thomas K, Dear S, Qiu L, Staden R, Berks M, Halloran N, Thierry-Mieg J, Hillier L, Sulston JE, Du Z, Durbin RM, Hawkins TL, Green P

[Nature, 1992]

The long-term goal of this project is the elucidation of the complete sequence of the Caenorhabditis elegans genome. During the first year methods have been developed and a strategy implemented that is amenable to large-scale sequencing. The three cosmids sequenced in this initial phase are surprisingly rich in genes, many of which have mammalian homologues.AD - MRC Laboratory of Molecular Biology, Cambridge, UK.FAU - Sulston, JAU - Sulston JFAU - Du, ZAU - Du ZFAU - Thomas, KAU - Thomas KFAU - Wilson, RAU - Wilson RFAU - Hillier, LAU - Hillier LFAU - Staden, RAU - Staden RFAU - Halloran, NAU - Halloran NFAU - Green, PAU - Green PFAU - Thierry-Mieg, JAU - Thierry-Mieg JFAU - Qiu, LAU - Qiu LAU - et al.LA - engPT - Journal ArticleCY - ENGLANDTA - NatureJID - 0410462RN - 0 (Cosmids)SB - IM

Stefano Canevascini et al. (2005) International Worm Meeting "Characterization of Agrin in C. elegans. ."

Ruth Chiquet-Ehrismann, Ana Hrus, Gordon Lau, Stefano Canevascini

[International Worm Meeting, 2005]

Agrin is a heparan sulfate proteoglycan important for development and tissue integrity in vertebrates. A splice form enriched in muscles is secreted into the basal lamina where it binds laminins and a-dystroglycan contributing to stabilize the connection between the extracellular matrix and the muscle cytoskeleton. Neuronal-specific splice forms expressed in cholinergic neurons are secreted into the synaptic cleft at the neuromuscular junctions and induce Acetylcholine Receptor clustering on the postsynaptic membrane. Finally, increasing evidence suggests that Agrin interacts with growth factors to mediate intercellular signaling. To investigate agrin function at a genetic level and to isolate novel interacting factors , we adopted the nematode C. elegans as model organism. The worm has a single agrin gene encoding a 1474 aa polypeptide that shares high homology with its vertebrate homologues. Inactivation of the agrin gene in the nematode by feeding and injecting dsRNA or by expressing a hairpin specifically in muscles or neurons of the animal has not revealed any obvious phenotype. A putative null mutant, eg1770, shows a slight resistance to aldicarb and levamisol and rescues the hypersensitivity to aldicarb of the dys-1(cx18) and dyb-1(cx36) mutants. Experiments could not support any genetic interaction between agrin(eg1770) and hlh-1(cc561), cle-1(cg120), unc-52(e444), unc-52(e1421), unc-52(gk3), nid-1(cg119), egl-20(mu39), unc-5(e152), unc-129(ev554), clr-1(e1745), lev-1(e211), and npr-1(g320). Agrin::gfp transcriptional fusions resulted in strong expression of the marker in four neurons in the head and in the nine buccal epidermal cells of the adult. Monoclonal antibodies raised against the C-terminus of the protein stain the basal lamina around the pharynx and some synapse-like structures in the nerve ring.

Vassilieva LL et al. (1999) Genetics "The rate of spontaneous mutation for life-history traits in Caenorhabditis elegans."

Vassilieva LL, Lynch M

[Genetics, 1999]

Spontaneous mutations were accumulated in 100 replicate lines of Caenorhabditis elegans over a period of approximately 50 generations. Periodic assays of these lines and comparison to a frozen control suggest that the deleterious mutation rate for typical life-history characters in this species is at least 0.05 per diploid genome per generation, with the average mutational effect on the order of 14% or less in the homozygous state and the average mutational heritability approximately 0.0034. While the average mutation rate per character and the average mutational heritability for this species are somewhat lower than previous estimates for Drosophila, these differences can be reconciled to a large extent when the biological differences between these species are taken into consideration.AD - Department of Biology, University of Oregon, Eugene, Oregon 97403, USA.larissa@darkwing.uoregon.eduFAU - Vassilieva, L LAU - Vassilieva LLFAU - Lynch, MAU - Lynch MLA - engID - RO1-GM36827/GM/NIGMSPT - Journal ArticleCY - UNITED STATESTA - GeneticsJID - 0374636SB - IM

Li X et al. (2022) Elife "The C. elegans gonadal sheath Sh1 cells extend asymmetrically over a differentiating germ cell population in the proliferative zone."

Miller C, Singh N, Gordon KL, Sosseh B, Washington I, Li X

[Elife, 2022]

The Caenorhabditis elegans adult hermaphrodite germline is surrounded by a thin tube formed by somatic sheath cells that support germ cells as they mature from the stem-like mitotic state through meiosis, gametogenesis, and ovulation. Recently, we discovered that the distal Sh1 sheath cells associate with mitotic germ cells as they exit the niche Gordon et al., 2020. Here, we report that these sheath-associated germ cells differentiate first in animals with temperature-sensitive mutations affecting germ cell state, and stem-like germ cells are maintained distal to the Sh1 boundary. We analyze several markers of the distal sheath, which is best visualized with endogenously tagged membrane proteins, as overexpressed fluorescent proteins fail to localize to distal membrane processes and can cause gonad morphology defects. However, such reagents with highly variable expression can be used to determine the relative positions of the two Sh1 cells, one of which often extends further distal than the other.

Jungsoo Lee et al. (2007) International Worm Meeting "Chronic effects of Ethanol in C. elegans."

Steven L. McIntire, Jungsoo Lee

[International Worm Meeting, 2007]

Ethanol can affect multiple signaling pathways. Some of these pathways have been implicated in acute or chronic behavioral responses to ethanol (Diamond and Gordon, 1997). Ethanol alters the behavioral responses of C. elegans at the same tissue concentrations that cause intoxication in humans (Davies et al., 2003). Similar molecular pathways appear to contribute to the acute neurodepressive effects of ethanol that are observed in C. elegans and mammalian systems. Ethanol exposure during development causes a variety of morphological changes and a retardation of growth. We are interested in identifying the molecular pathways that contribute to the developmental and behavioral defects that are observed after chronic ethanol exposure. We have observed that ethanol inhibits the growth of wild-type animals. To better understand the mechanisms contributing to this effect, we carried out screens for mutants resistant to the chronic effects of ethanol. We have screened 5,000 haploid genomes and have isolated 14 candidates showing resistance to ethanol inhibition of growth. Several mutants are also resistant to acute effects of ethanol on locomotion and egg laying. Some of the mutants have a defect in the acute tolerance that occurs during a continuous ethanol exposure. None of the mutants have an obvious behavioral phenotype in the absence of ethanol. One possibility is that chronic ethanol induces oxidative stress by enhancing reactive oxygen species (ROS) formation or by decreasing oxidative defenses (Sun et al., 2001). To assess the relationship between resistance to ethanol and oxidative stress, we examined sensitivity of the mutants to paraquat. A subset of the mutants is also resistant to paraquat. We have mapped two mutants to the center of chromosome X and are currently in the process of cloning these genes. Reference: Diamond I and Gordon AS (1997). Cellular and molecular neuroscience of alcoholism. Physiol Rev. 77(1):1-20. Review Davies AG et al. (2003). A central role of the BK potassium channel in behavioral responses to ethanol in C. elegans. Cell 115(6):655-66.

Mondol V et al. (2012) Curr Top Dev Biol "Let's make it happen: the role of let-7 microRNA in development."

Mondol V, Pasquinelli AE

[Curr Top Dev Biol, 2012]

Noncoding RNAs have emerged as an integral part of posttranscriptional gene regulation. Among that class of RNAs are the microRNAs (miRNAs), which posttranscriptionally regulate target mRNAs containing complementary sequences. The broad presence of miRNAs in lower eukaryotes, plants, and mammals highlights their importance throughout evolution. MiRNAs have been shown to regulate many pathways, including development, and disruption of miRNA function can lead to disease (Ivey and Srivastava, 2010; Jiang et al., 2009). Although the first miRNA genes were discovered in the nematode, Caenorhabditis elegans, almost 20 years ago, the field of miRNA research began when they were found in multiple organisms a little over a decade ago (Lagos-Quintana et al., 2001; Lau et al., 2001; Lee and Ambros, 2001; Lee et al., 1993; Pasquinelli et al., 2000; Wightman et al., 1993). Here, we review one of the first characterized miRNAs, let-7, and describe its role in development and the intricacies of its biogenesis and function.

Legouis R et al. (2000) Nat Cell Biol "LET-413 is a basolateral protein required for the assembly of adherens junctions in Caenorhabditis elegans."

Sookhareea S, Gansmuller A, Legouis R, Baillie DL, Bosher JM, Labouesse M

[Nat Cell Biol, 2000]

Epithelial cells are polarized, with apical and basal compartments demarcated by tight and adherens junctions. Proper establishment of these subapical junctions is critical for normal development and histogenesis. We report the characterization of the gene let-413 which has a critical role in assembling adherens junctions in Caenorhabditis elegans. In let-413 mutants, adherens junctions are abnormal and mislocalized to more basolateral positions, epithelial cell polarity is affected and the actin cytoskeleton is disorganized. The LET-413 protein contains one PDZ domain and 16 leucine-rich repeats with high homology to proteins known to interact with small GTPases. Strikingly, LET-413 localizes to the basolateral membrane. We suggest that LET-413 acts as an adaptor protein involved in polarizing protein trafficking in epithelial cells.AD - Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS/INSERM/ULP, Illkirch, France.FAU - Legouis, RAU - Legouis RFAU - Gansmuller, AAU - Gansmuller AFAU - Sookhareea, SAU - Sookhareea SFAU - Bosher, J MAU - Bosher JMFAU - Baillie, D LAU - Baillie DLFAU - Labouesse, MAU - Labouesse MLA - engSI - GENBANK/AJ276590PT - Journal ArticleCY - ENGLANDTA - Nat Cell BiolJID - 100890575RN - 0 (Helminth Proteins)RN - 0 (LET-413 protein)SB - IM

McIntire SL et al. (1993) Nature "The GABAergic nervous system of Caenorhabditis elegans."

Horvitz HR, Kaplan JM, McIntire SL, Jorgensen EM

[Nature, 1993]

gamma-Aminobutyric acid (GABA) is the most abundant inhibitory neurotransmitter in vertebrates and invertebrates. GABA receptors are the target of anxiolytic, antiepileptic and antispasmodic drugs, as well as of commonly used insecticides. How does a specific neurotransmitter such as GABA control animal behaviour? To answer this question, we identified all neurons that react with antisera raised against the neurotransmitter GABA in the nervous system of the nematode Caenorhabditis elegans. We determined the in vivo functions of 25 of the 26 GABAergic neurons by killing these cells with a laser microbeam in living animals and by characterizing a mutant defective in GABA expression. On the basis of the ultrastructurally defined connectivity of the C. elegans nervous system, we deduced how these GABAergic neurons act to control the body and enteric muscles necessary for different behaviours. Our findings provide evidence that GABA functions as an excitatory as well as an inhibitory neurotransmitter.AD - Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, 02139.FAU - McIntire, S LAU - McIntire SLFAU - Jorgensen, EAU - Jorgensen EFAU - Kaplan, JAU - Kaplan JFAU - Horvitz, H RAU - Horvitz HRLA - engPT - Journal ArticleCY - ENGLANDTA - NatureJID - 0410462RN - 56-12-2 (gamma-Aminobutyric Acid)SB - IM

Walhout AJM et al. (2000) Science "Protein interaction mapping in C. elegans using proteins involved in vulval development."

Sordella R, Hartley JL, Lu WX, Thierry-Mieg N, Walhout AJM, Brasch MA, Temple GF, Vidal MI

[Science, 2000]

Protein interaction mapping using large-scale two-hybrid analysis has been proposed as a way to functionally annotate large numbers of uncharacterized proteins predicted by complete genome sequences. This approach was examined in Caenorhabditis elegans, starting with 27 proteins involved in vulval development. The resulting map reveals both known and new potential interactions and provides a functional annotation for approximately 100 uncharacterized gene products. A protein interaction mapping project is now feasible for C. elegans on a genome-wide scale and should contribute to the understanding of molecular mechanisms in this organism and in human diseases.AD - Massachusetts General Hospital Cancer Center, Charlestown, MA 02129, USA.FAU - Walhout, A JAU - Walhout AJFAU - Sordella, RAU - Sordella RFAU - Lu, XAU - Lu XFAU - Hartley, J LAU - Hartley JLFAU - Temple, G FAU - Temple GFFAU - Brasch, M AAU - Brasch MAFAU - Thierry-Mieg, NAU - Thierry-Mieg NFAU - Vidal, MAU - Vidal MLA - engID - 1 R21 CA81658 A 01/CA/NCIID - 1 RO1 HG01715-01/HG/NHGRIPT - Journal ArticleCY - UNITED STATESTA - ScienceJID - 0404511RN - 0 (Genetic Vectors)RN - 0 (Helminth Proteins)RN - 0 (LIN-35 protein)RN - 0 (LIN-53 protein)RN - 0 (Repressor Proteins)RN - 0 (Retinoblastoma Protein)SB - IM

Reboul J et al. (2001) Nat Genet "Open-reading-frame sequence tags (OSTs) support the existence of at least 17,300 genes in C. elegans."

Doucette-Stamm L, Lamesch PE, Reboul J, Temple GF, Hartley JL, Brasch MA, Hill DE, Vaglio P, Thierry-Mieg N, Shin-i T, Lee H, Moore T, Vandenhaute J, Kohara Y, Vidal M, Jackson C, Thierry-Mieg J, Tzellas N, Thierry-Mieg D, Hitti J

[Nat Genet, 2001]

The genome sequences of Caenorhabditis elegans, Drosophila melanogaster and Arabidopsis thaliana have been predicted to contain 19,000, 13,600 and 25,500 genes, respectively. Before this information can be fully used for evolutionary and functional studies, several issues need to be addressed. First, the gene number estimates obtained in silico and not yet supported by any experimental data need to be verified. For example, it seems biologically paradoxical that C. elegans would have 50% more genes than Drosophilia. Second, intron/exon predictions need to be tested experimentally. Third, complete sets of open reading frames (ORFs), or "ORFeomes," need to be cloned into various expression vectors. To address these issues simultaneously, we have designed and applied to C. elegans the following strategy. Predicted ORFs are amplified by PCR from a highly representative cDNA library using ORF-specific primers, cloned by Gateway recombination cloning and then sequenced to generate ORF sequence tags (OSTs) as a way to verify identity and splicing. In a sample (n=1,222) of the nearly 10,000 genes predicted ab initio (that is, for which no expressed sequence tag (EST) is available so far), at least 70% were verified by OSTs. We also observed that 27% of these experimentally confirmed genes have a structure different from that predicted by GeneFinder. We now have experimental evidence that supports the existence of at least 17,300 genes in C. elegans. Hence we suggest that gene counts based primarily on ESTs may underestimate the number of genes in human and in other organisms.AD - Dana-Farber Cancer Institute and Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.FAU - Reboul, JAU - Reboul JFAU - Vaglio, PAU - Vaglio PFAU - Tzellas, NAU - Tzellas NFAU - Thierry-Mieg, NAU - Thierry-Mieg NFAU - Moore, TAU - Moore TFAU - Jackson, CAU - Jackson CFAU - Shin-i, TAU - Shin-i TFAU - Kohara, YAU - Kohara YFAU - Thierry-Mieg, DAU - Thierry-Mieg DFAU - Thierry-Mieg, JAU - Thierry-Mieg JFAU - Lee, HAU - Lee HFAU - Hitti, JAU - Hitti JFAU - Doucette-Stamm, LAU - Doucette-Stamm LFAU - Hartley, J LAU - Hartley JLFAU - Temple, G FAU - Temple GFFAU - Brasch, M AAU - Brasch MAFAU - Vandenhaute, JAU - Vandenhaute JFAU - Lamesch, P EAU - Lamesch PEFAU - Hill, D EAU - Hill DEFAU - Vidal, MAU - Vidal MLA - engID - R21 CA81658 A 01/CA/NCIID - RO1 HG01715-01/HG/NHGRIPT - Journal ArticleCY - United StatesTA - Nat GenetJID - 9216904SB - IM