Juliet C Coates et al. (2001) International C. elegans Meeting "Neurons regulating social feeding behaviour in C. elegans"

Juliet C Coates, Mario De Bono

[International C. elegans Meeting, 2001]

The C. elegans npr-1 gene encodes a seven transmembrane receptor related to mammalian neuropeptide Y receptors. In mammals, neuropeptide Y signalling regulates food intake and alcohol tolerance. In C. elegans , natural variation at the npr-1 locus determines whether worms behave in a social or a solitary manner in the presence of food. We seek to identify the neuronal circuits regulating this foraging behaviour. To begin to address this question, we identified the neurons that express npr-1 . A functional NPR-1::GFP fusion protein under the control of the npr-1 promoter is expressed in about 20 types of neurons. These include paired and unpaired neurons in the head and tail, and also a subset of ventral nerve cord motorneurons. We then asked when NPR-1 expression is required to suppress social behaviour. Transient expression of NPR-1::GFP in adult worms using the heat shock promoter suppresses social behaviour. This suggests that npr-1 is required acutely rather than for development of the nervous system. In addition, expression of the solitary form of NPR-1 in just four of the 20 types of neurons that express NPR-1 can suppress the social behaviour of npr-1(null) worms strongly. Expression of NPR-1 in subsets of these neurons gives partial suppression. The data suggest that some neurons may act redundantly within a network, whereas other neurons have an additive effect on suppressing social behaviour. Loss-of-function mutations in the eat-4 glutamate transporter (1) also suppress social behaviour, suggesting that the glutamatergic activity of certain eat-4 -expressing neurons may be required for worms to be social. We are trying to discover which neurons are required for this effect by adding back wild type eat-4 cDNA to subsets of neurons in eat-4; npr-1 mutants and looking for a rescue of social behaviour in these animals. 1. Lee RYN, Sawin ER, Chalfie M, Horvitz HR, Avery L; J. Neurosci 19: 159-167 (1999)

Sokolowski MB (2002) Nature "Neurobiology: social eating for stress."

Sokolowski MB

[Nature, 2002]

Behavioral ecologists have shown that many animals form social groups in conditions. Neurobiological evidence for this behaviour has now been discovered in the nematode worm, Caenorhabditis elegans. On pages 899 and 925 of this issue, de Bono et al. and Coates and de Bono present striking results on the genetic, molecular and neural mechanisms underlying nematode social feeding. These discoveries provide tantalizing insights into the effects of stress in social groupings.

Beech RN et al. (2010) Trends Parasitol "Nematode parasite genes: what's in a name?"

Dent JA, Neveu C, Wolstenholme AJ, Beech RN

[Trends Parasitol, 2010]

The central theme of Shakespeare's Romeo and Juliet is that names are meaningless, artificial constructs, detached from any underlying reality. By contrast, we argue that a well chosen gene name can concisely convey a wealth of relevant biological information. A consistent nomenclature adds transparency that can have a real impact on our understanding of gene function. Currently, genes in parasitic nematodes are often named ad hoc, leading to confusion that can be resolved by adherence to a nomenclature standard adapted from Caenorhabditis elegans. We demonstrate this with ligand-gated ion-channels and propose that the flood of genome data and differences between parasites and the free living C. elegans will require modification of the standard.

Hongtao Qin et al. (2003) International Worm Meeting "AHR-1, the C. elegans aryl hydrocarbon receptor, regulates neuronal development."

Jo Anne Powell-Coffman, Hongtao Qin

[International Worm Meeting, 2003]

The mammalian aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor, and it mediates the toxic effects of dioxins and related compounds. Toxicological studies suggest that inappropriate activation of AHR causes a range of pathologies, including neurological defects. AHR and its nuclear dimerization partner, ARNT, are known to bind to specific DNA sequences to regulate the expression of target genes. However, the role of AHR during normal neuronal development is not understood. The C. elegansorthologs of AHR and ARNT are ahr-1and aha-1, respectively. ahr-1:GFP is expressed in a subset of neurons. These cells represent multiple neuronal subtypes and include the descendents of the Q neuroblasts, certain interneurons, and the neurons that directly contact pseudocoelomic fluid in the body cavity. Animals lacking ahr-1function have specific defects in neuronal differentiation, as evidenced by changes in gene expression, aberrant cell migration, axon branching, or supernumerary neuronal processes. Genetic analyses support a model in which AHR-1 executes its developmental functions as an AHR-1:AHA-1 transcriptional complex. Specifically, dorsal migration of the SDQR interneuron requires the functions of both ahr-1and its transcription factor dimerization partner aha-1. Additional analyses of GFP reporter genes indicate that AHR-1 expression is regulated by the UNC-86 POU domain transcription factor in some cell types. In AQR, PQR, and URX, AHR-1 activates expression of the gcy-32soluble guanylyl cyclase gene. Coates and de Bono recently demonstrated that these neurons mediate social feeding behavior. Interestingly, a strong loss-of-function mutation in ahr-1partially suppresses social feeding behavior in npr-1-deficient animals. To further characterize ahr-1function in these neurons, we are analyzing the expression of other cell-type-specific markers in ahr-1-and aha-1-deficient animals. Powell-Coffman et al. (1998) PNAS 95 p.2844; Coates and de Bono (2002) Nature 419 p.925

Zhao Y et al. (2007) BMC Genomics "Poly-G/poly-C tracts in the genomes of Caenorhabditis."

Zhao Y, O'Neil NJ, Rose AM

[BMC Genomics, 2007]

ABSTRACT: BACKGROUND: In the genome of Caenorhabditis elegans, homopolymeric poly-G/poly-C tracts (G/C tracts) exist at high frequency and are maintained by the activity of the DOG-1 protein. The frequency and distribution of G/C tracts in the genomes of C. elegans and the related nematode, C. briggsae were analyzed to investigate possible biological roles for G/C tracts. RESULTS: In C. elegans, G/C tracts are distributed along every chromosome in a non-random pattern. Most G/C tracts are within introns or are close to genes. Analysis of SAGE data showed that G/C tracts correlate with the levels of regional gene expression in C. elegans. G/C tracts are over-represented and dispersed across all chromosomes in another Caenorhabditis species, C. briggase. However, the positions and distribution of G/C tracts in C. briggsae differ from those in C. elegans. Furthermore, the C. briggsae dog-1 ortholog CBG19723 can rescue the mutator phenotype of C. elegans dog-1 mutants. CONCLUSIONS: The abundance and genomic distribution of G/C tracts in C. elegans, the effect of G/C tracts on regional transcription levels, and the lack of positional conservation of G/C tracts in C. briggsae suggest a role for G/C tracts in chromatin structure but not in the transcriptional regulation of specific genes.

Mario de Bono (2003) International Worm Meeting "Evolutionary and behavioural perspectives on nematode aggregation"

Mario De Bono

[International Worm Meeting, 2003]

Aggregation behaviour has been reported in many species of nematodes, including vertebrate gut parasites such as Trichostrongylus colubriformis1(Strongylida), plant parasites such as Tylenchorhynchus martini2 (Tylenchida) and free-living species such as C. elegans3(Rhabditida). This prompted us to look for aggregation behaviour in other nematode species. Under our standard assay conditions, wild isolates of C. remanei (n=6 isolates) all aggregated to similar extents as social isolates of C. elegans. In contrast, most C. briggsae isolates (n=8) showed only weak aggregation behaviour, and one isolate, AF16(Gujarat), behaved like a C. elegans solitary feeder. The Caenorhabditis sp. CB5161 also behaved like a solitary feeder. Interestingly, all these strains encode NPR-1 215F, the NPR-1 isoform associated with social feeding in C. elegans. This suggests that the genetically dominant npr-1 215V allele arose in C. elegans by a gain-of-function change. It also suggests that other changes, either in npr-1 or in other genes, account for natural variation in aggregation behaviour in these strains. Outside Caenorhabditis, I have seen aggregation behaviour in Rhabditis blumi (DF5010), Rhabditella axei (DF5006), Pellioditis typica (DF5025) and Pelodera teres (EM437). Further work is needed to establish if these behaviours are homologous or the result of convergent evolution. However one possibility is that the ability to aggregate is ancient in nematodes. This would be consistent with our genetic studies, which suggest remarkable complexity in the regulation of aggregation behaviour4,5. To gain insights into how C. elegans aggregate, we are filming social and solitary animals and quantitatively comparing their behaviours as they feed and encounter each other on the E. coli lawn. Since E. coli may not be an important source of food for C. elegans in the wild, we have also examined behaviour on soil bacteria more likely to be a dietary staple of the worm, including Pseudomonas paucimobilis, P. chlororaphis, P. putida, P. fluorescens, Agrobacterium radiobacter, Burkholderia cepacia, and B. subtilis. Social strains aggregated on all these bacterial species, whereas solitary animals did not. 1 Jenkins et al., 1986; Parasitology 93: 531-537; 2 McBride and Hollis 1966, Nature 211, 545-546; 3 Randy Cassada, WBG 9(3) 29; 4 de Bono et al., 2002, Nature 419: 899-903; 5 Coates and de Bono, Nature 419: 925-929.

Bhagwati P Gupta et al. (2002) West Coast Worm Meeting "Genetic analysis of the vulval mutants in C. briggsae"

Shahla Gharib, Bhagwati P Gupta, Paul W Sternberg, Jennifer X Li

[West Coast Worm Meeting, 2002]

To understand the evolution of developmental mechanisms, we are doing a comparative analysis of vulval patterning in C. elegans and C. briggsae. C. briggsae is closely related to C. elegans and has identical looking vulval morphology. However, recent studies have indicated subtle differences in the underlying mechanisms of development. The recent completion of C. briggsae genome sequence by the C. elegans Sequencing Consortium is extremely valuable in identifying the conserved genes between C. elegans and C. briggsae.

Antika TR et al. (2023) J Biol Chem "Sequence-specific targeting of C. elegans C-Ala to the D-loop of tRNAAla."

Horng JC, Hsu HL, Nazilah KR, Wang CC, Wang TL, Wang SC, Antika TR, Chuang TH, Chrestella DJ, Wang SW, Tseng YK, Pan HC

[J Biol Chem, 2023]

Alanyl-tRNA synthetase (AlaRS) retains a conserved prototype structure throughout its biology. Nevertheless, its C-terminal domain (C-Ala) is highly diverged and has been shown to play a role in either tRNA or DNA binding. Interestingly, we discovered that Caenorhabditis elegans cytoplasmic C-Ala (Ce-C-Ala_c) robustly binds both ligands. How Ce-C-Ala_c targets its cognate tRNA and whether a similar feature is conserved in its mitochondrial counterpart remain elusive. We show that the N- and C-terminal subdomains of Ce-C-Ala_c are responsible for DNA and tRNA binding, respectively. Ce-C-Ala_c specifically recognized the conserved invariant base G¹⁸ in the D-loop of tRNA^Ala through a highly conserved lysine residue, K934. Despite bearing little resemblance to other C-Ala domains, C. elegans mitochondrial C-Ala (Ce-C-Ala_m) robustly bound both tRNA^Ala and DNA and maintained targeting specificity for the D-loop of its cognate tRNA. This study uncovers the underlying mechanism of how C. elegans C-Ala specifically targets the D-loop of tRNA^Ala.

Blumenthal TE et al. (1994) Worm Breeder's Gazette "C. elegans U2AF 65."

Zorio DAR, Lea K, Blumenthal TE

[Worm Breeder's Gazette, 1994]

C. elegans U2AF65

David Yu et al. (2001) International C. elegans Meeting "Characterization of Several G protein-coupled Receptors for the Secretin Family of Neuropeptides"

David Yu, Edward Hedgecock

[International C. elegans Meeting, 2001]

The secretin family of neuropeptides includes several physiologically essential molecules: secretin, calcitonin, corticotrophin releasing factor, and glucagon. In humans, defects in receptors of the secretin family cause abnormal function in the liver and pancreas, leading to several gastrointestinal diseases. To better understand the molecular biology of these receptors, we have identified three novel genes in C. elegans that are possible orthologues to the human secretin family receptors using BLAST and ESTs: ZK643.3, C18B12.2, and C13B9.4. These genes exhibit a high level of conservation with mammalian and fly secretin family receptors. Amino acid alignments suggest ZK643.3 is homologous to human corticotrophin releasing factor receptor, C13B9.4 is homologous to human calcitonin receptor, and C18B12.2 is homologous to human secretin receptor (see poster by Mastwal and Hedgecock). Previous work has shown that ZK643.3 is expressed in the muscle cells of the head and in muscle cells that control opening and closing of the vulva (Coates, 1995). To further characterize this gene, we generated a ZK643.3 promoter::GFP fusion construct. We observed expression in head muscle cells and pharyngeal and ventral nerve cord neurons. RNAi and co-immunoprecipitation of ZK643.3, as well as C13B9.4 and C18B12.2 will provide further insight to the function of this secretin receptor family and identify interacting proteins.