Osana Y et al. (2000) Japanese Worm Meeting "Overall Morphology of the C. elegans Neural Circuit"

Oka K, Oshio K-i, Kawamura K, Omata K, Morita S, Osana Y

[Japanese Worm Meeting, 2000]

To study the overall structure of the C. elegans neural circuit, we have carried out cluster analyses on the basis of the neuronal-connectivity database constructed by Oshio et al. . The analyses regard on the connectional multiplicities of the chemical synapses and gap junctions, and the circuit is subjected to thresholds for the multiplicities. With decreasing the thresholds, the number of connections is increased, and the size of the largest neuronal cluster increases gradually until a prominent growth occurs, indicating that the natural circuit without thresholds is a supercritical network'. The critical point provides an index for the determination of an appropriate threshold from which the simplified backbone circuit is derived. We find that there are roughly four indepenent streams in the circuit. Each stream has indivisual functions such as mechanical sensation, chemotaxis, thermotaxis and so forth, and the neurons controlling these functions are specified in the backbone structures. We suggest that the collective properties of the neurons play essential roles for the circuit activity, and the global backbone circuit derived from our analyses explore the possibilities for future experimental studies.

Y Osana et al. (1999) International C. elegans Meeting "Neural Network Model for Touch Sensitivity in Caenorhabditis elegans"

S Morita, K Oshio, K Oka, Y Funabashi, Y Osana, M Hagiwara, K Kawamura

[International C. elegans Meeting, 1999]

In this research, we propose an artificial neural network model for touch sensitivity in Caenorhabditis elegans . The neural circuit for touch sensitivity in C.elegans has been examined in detail and is constituted by 66 neurons grouped in 14 classes. The proposed neural network model is directory inspired from the real connectivity data in C. elegans and is based on one of the suitable artificial neural networks, Boltzmann machine. This model has visible units (input units and output units) and invisible units (hidden units). In the nerve system of C. elegans , we considered that the sensory neurons which receive touch stimulus correspond to the input units, the interneurons correspond to hidden units, and the motor neurons correspond to output units. In this research, for simplicity, each unit in the proposed neural network model corresponds to a neuron class instead of a neuron. That is, the neural network model is composed of four input units (ALM, AVM, PLM, PVM), five hidden units (AVA, AVB, AVD, LUA, PVC) and five output units (AS, DA, DB, VA, VB). The values of connection weights which correspond to synapses are determined under the constraint of the connectivity observed in C. elegans by Hebbian-like learning algorithm as same as in the conventional Boltzmann machine . We carried out a series of computer simulations and showed that the proposed model replicates the similar behaviors observed in the real C.elegans . In the simulations, after the values of connection weights in the proposed model are determined, when the sensory neurons for anterior touch ALM and AVM are stimulated, the motor neurons for backward movement AS, DA and VA are excited. In the same way, when the sensory neurons for posterior touch PLM and PVM are stimulated, the motor neurons for forward movement DB and VB are excited. We also compared the lesion test in the proposed model with the laser ablation test in the real C.elegans . As in real C.elegans , the simulation results show that AVD and PVC interneurons are essential for backward and forward movement, respectively.

Sato, Manami et al. (2015) International Worm Meeting "Expression pattern of C. elegans Y RNA homologs."

Ushida, Chisato, Kihara, Shinya, Sato, Manami

[International Worm Meeting, 2015]

Y RNA is a small structured ncRNA of about 100 nt in length. This RNA binds to Ro60 protein, which is a target of autoimmune disease antibody in patients with systemic lupus erythematosus and Sjogren's syndrome. Several lines of evidence suggest that the role of Y RNA and Ro60 function in the quality control of structured ncRNAs in cells under stress conditions. It is also indicated that vertebrate Y RNAs function in the initiation of DNA replication without Ro60. However, the molecular mechanisms of these functions and the contribution of Ro60/Y RNP to the autoimmune disease are still unclear. C. elegans genome encodes one Ro60 homolog (ROP-1) and 19 Y RNA homologs (1 CeY RNA and 18 sbRNAs). Other animals also have several Y RNA homologs, but C. elegans is the first example which has more than 5 Y RNA homologs encoded in the genome. Here we show the expression pattern and the cellular localization of these Y RNA homologs in C. elegans examined by the RNA fluorescent in situ hybridization (RNA-FISH). The signals of 14 homologs were detected in the intestinal cytoplasm. The signals of two other homologs were detected in the germ cytoplasm. The remaining three could not be detected, probably because they present in too low abundance to be detected by RNA-FISH. All 19 Y RNA homologs have the structural elements required for the binding of ROP-1. In other organisms, Ro60 binding stabilizes Y RNAs in cells. To know whether C. elegans Y RNA homologs also stabilized by the presence of ROP-1, we examined RNA-FISH of the Y RNA homologs against a mutant strain MQ470, which has a transposon insertion in the middle of the ROP-1 gene and lacks ROP-1 proteins in the cell. As expected, all Y RNAs examined so far decreased extensively. These were confirmed by northern hybridization. The results suggest that several C. elegans Y RNA homologs are expressed in a tissue-specific manner and most Y RNA homologs are stabilized by ROP-1 binding as well as those in other organisms.

Iwasaki Y et al. (2000) Japanese Worm Meeting "Study of Excitatory and Inhibitory Synaptic Connections in Neural Circuit for Touch-induced and Tap Responses"

Iwasaki Y, Gomi S, Osana Y

[Japanese Worm Meeting, 2000]

In order to predict the signs (excitatory or inhibitory) of connections between neurons, numerical studies are performed on the neural circuit of C.elegans for the touch-induced and the tap response. Neurons are modeled simply as McCulloch-Pitts neurons. Among all possible ways of assigning the signs for each connection, we select out the networks which satisfy the correct neural input-output relations of both touch-induced and tap responses.Experimental knowledge on the effects of laser ablation of neurons are also used as conditions for the selection of the networks. By examining the average structure of the remained (selected) networks, some of the signs of connections in the networks may be unambiguously predicted. These results are compared to the results of the study which use the process of learning for producing the neural networks with correct input-output relations.

Nancy L Price et al. (2003) International Worm Meeting "The utilization of Caenorhabditis briggsae as a host model to study bacterial pathogenesis"

Ann M Rose, Nancy L Price

[International Worm Meeting, 2003]

Caenorhabditis elegans has now been established as a host model for studies of infectivity by bacterial pathogens including Pseudomonas aeruginosa, Salmonella typhimurium, Burkholderia pseudomallei, and Enterococcus faecalis. However, virulence determinants of bacterial pathogens are regulated by temperature and environmental conditions, thereby limiting the use of C. elegans which cannot survive in temperatures higher than 25oC. This study shows that the related species, C. briggsae survives better than C. elegans on bacterial culture media at higher temperatures and describes the effects on C. briggsae of mammalian enteric pathogens, primarily Yersinia enterocolitica. C. briggsae grown on Y. enterocolitica accumulated bacteria in the gastrointestinal tract of the worm, resulting in decreased life-span and progeny fitness in a depleted-calcium environment. The mechanisms of the interaction are as yet unknown as both virulent and avirulent strains of Y. enterocolitica displayed the similar results. Investigations were undertaken to examine whether the shortened life span could be attributed to starvation, toxicity, or possible infection. Starvation effects was determined not to be the sole cause of pre-mature worm death as C. briggsae grown on Y. enterocolitica survived several days longer than starved worms. A bacterial mixing experiment using both Y. enterocolitica and E. coli OP50 shortened the worm life span compared to feeding on Y. enterocolitica alone, suggesting a possible toxic effect. However worms feeding on Y. enterocolitica and later shifted to E. coli OP50 resulted in reversion of the survival curve to that of worms feeding on E. coli OP50 alone, indicating that the detrimental effect of Y. enterocolitica was reversible. Fluorescent labeling of bacterial strains with a lacZ-GFP reporter gene demonstrated that Y. enterocolitica, but not E. coli OP50, is retained in the gut, a result which is compatible with a molecular interaction between Y. enterocolitica and nematode cellular components. These findings suggest that Y. enterocolitica may cause an infection within the nematode gastrointestinal tract and provide an assay for genetic dissection of the molecular basis of pathogenesis.

Michael Muller et al. (2006) European Worm Meeting "A Knock-Out of the Small Non-Coding Y RNA in C. elegans"

Michael Muller, Michael Jantsch, Gunter Steiner, Verena Jantsch

[European Worm Meeting, 2006]

Michael Mller1, Verena Jantsch2, Michael Jantsch2, Gnter Steiner1. Ro ribonucleoproteins (RNPs) are small cytoplasmic particles of unknown function that have been found in all eukaryotes except yeasts. The core structure of human Ro RNPs is composed of one molecule of Y RNA to which the 60 kD Ro protein (Ro60) and La protein are stably bound. Ro RNPs are predominant target structures in the autoimmune diseases Systemic Lupus Erythematosus and Sjgrens syndrome and autoantibodies to Ro60 and La, can be frequently found in the sera of patients suffering from these diseases. The Ro60 protein is highly conserved in higher eukaryotes and the phenotype of a disruption of the gene encoding the C. elegans Ro60 homologue (rop-1) was characterized (Labb et al. Genetics 1999, PNAS 2000). A decrease in Y RNA levels and a higher frequency of misfolded ribosome-associated 5s rRNAs was observed in rop-1 mutant worms. Rop-1 mutants were also shown to be defective in the formation of dauer larvae. Recently the structure of Ro60 was established (Stein et al. Cell 2005) and it was shown that the Y RNA binding site of Ro60 overlaps with the binding site for misfolded RNAs. These results suggest a regulatory role the Y RNA for the binding of misfolded RNAs to Ro60.. In humans and most other vertebrates four different Y RNAs are expressed, while in the nematode C. elegans only one Y RNA species has been found. The C. elegans Y RNA is highly conserved in its structure and most closely related to human Y3 RNA. Yet it differs from other eukaryotic Y RNAs as it is missing a 3 extension to which La is binding (van Horn et al. RNA 1995). To learn more about the function of Y RNAs, we took advantage of the fact that the C. elegans genome contains only a single Y RNA gene (yrn-1). We generated a knock-out line of the C. elegans Y RNA by the method of gene targeting by biolistic transformation. Yrn-1 is located within an intron of an uncharacterized, protein-coding gene. We modified a method for gene disruption (Berezikov et al. Nucleic Acids Res. 2004) in our approach, as we deleted yrn-1 in our knock-out construct rather than disrupting the locus, which could have resulted in a double knock-out.. Yrn-1 mutant worms do not display any obvious morphological phenotype. However, preliminary results indicate that Y RNA deficient worms show a delayed response to chemoattractants. Future experiments are planned to elucidate the role of the Y RNA in damage repair upon UV induced damage, in coping with various forms of stress and in the dauer formation pathway.

Sophie Jarriault et al. (2007) International Worm Meeting "The Y to PDA cell identity change in C. elegans : an in vivo model to study cell plasticity."

Yannick Schwab, Iva Greenwald, Sophie JARRIAULT

[International Worm Meeting, 2007]

The question of trans-differentiation or how a commited cell can change its identity has important implications ranging from organ regeneration to cancer. The lineage of the nematode C. elegans has identified a few cells that change their fates as the worm develops (1, 2), but this interesting observation has never been studied further. We are interested in understanding the molecular events underlying the Y to PDA cell transformation in C. elegans. Y is an epithelial cell that is part of the rectum in young larvae. It subsequentely moves anteriorly and becomes PDA, a motor-neuron which has a characteristic axonal projection . We have developed a set of useful molecular markers that allow to track the Y to PDA transformation and characterised the steps involved in this process, which we timed precisely with respect to the development of the somatic gonad. We have characterised the epithelial features of the Y cell at the ultrastructural level by electron-microscopy and we have examined the expression of cell fate markers in both cells. In addition, we showed that Y''s identity change does not require genes known to affect the developmental timing in C. elegans and we found that cell fusion, a possible mechanism invoked for trans-differentiation in vertebrates, does not contribute to the Y to PDA transformation. Finally, we have examined the importance of cell to cell interactions for the Y to PDA transformation by cell ablation experiments and studies of mutants affecting it, and what makes the Y cell competent to change its identity. We believe that this system is a powerful model to study cell plasticity in vivo, and we will discuss the results of our findings at the meeting. 1. J. E. Sulston, H. R. Horvitz, Dev Biol 56, 110-56 (Mar, 1977). 2. J. E. Sulston, J. G. White, Dev Biol 78, 577-97 (Aug, 1980).

Valeria Pavet et al. (2008) European Worm Meeting "Deciphering epithelial cell plasticity in C. elegans"

Iva Greenwald, Nadege Vaucamps, Sophie JARRIAULT, Valeria Pavet, Yannick Schwab

[European Worm Meeting, 2008]

Understanding how a differentiated cell is able to change its identity. and give rise to a different kind of differentiated cell - process called. transdifferentiation (or TD)- is a challenging task, and the results. obtained will have a profound impact in both basic and clinical science.. In C. elegans, an epithelial cell named "Y" is born in the embryo and is. one of the six epithelial cells that form the rectum in a young larva.. During the second larval stage, Y detaches from the rectum, migrates. anteriorly and becomes a motor-neuron named "PDA", without cell division.. We have shown that the Y-to-PDA conversion represents a bona fide TD. event. Indeed, we have demonstrated that Y presents exclusively. epithelial features while being a part of the rectum, and that these. characteristics are lost and replaced by purely neuronal ones after its. TD into PDA. We have performed an initial characterization of this. process, using genetics and cell ablation to explore factors pertaining. to competence, lineage, and local environment. We found that. transdifferentiation does not depend on fusion with a neighbouring cell. or require migration of Y away from the rectum; that other rectal. epithelial cells are not competent to transdifferentiate; and that. transdifferentiation requires the EGL-5 and SEM-4 transcription factors. and LIN-12/Notch signalling. In order to identify and characterize the. genes and the genetic cascade(s) involved in each step of the Y-to-PDA. TD, we have performed a forward genetic screen for mutants that do not. have a PDA neuron. The mutants obtained fall into two clearly. distinguishable morphological classes: mutants having a persistent. epithelial Y cell that did not transdifferentiate and mutants where an. epithelial Y cell is no longer recognizable. We have started to map and. characterize mutants belonging to the two morphological groups and use. them to examine the intermediate steps of TD. We believe that this system. will allow us to identify the mechanisms underlying this TD event and to. propose a model of how cell plasticity proceeds.

Chiba, T. et al. (2019) International Worm Meeting "Expression pattern of C. elegans Y RNA homologs and two different RNAs from cel-7."

Huanyu, F., Kihara, S., Ushida, C., Sato, M., Chiba, T.

[International Worm Meeting, 2019]

Ro60/Y RNP was found as an autoantigen from human autoimmune disease patients with systemic lupus erythematosus and Sjogren's syndrome. The function was suggested to be the quality control of small structured ncRNAs such as 5S rRNA and U2 snRNA. Interestingly, Ro60/Y RNP was shown to be involved in the stress response of cells and bodies. However, the molecular mechanism of Ro60/Y RNP function and the relation between the function and the stress response are not yet clear. C. elegans has a Ro60 homolog, ROP-1, and 19 Y RNA homologs. Previously we reported the expression pattern and the subcellular localization of Y RNA homologs analyzed by FISH experiments using the antisense RNA probes. Because some RNAs are highly homologous to the others, they were difficult to distinguish in FISH. Therefore, the expressions of Y RNA homologs were determined by northern hybridization using the oligonucleotide DNA probes that had the antisense sequence of the loop region, which was unique in each Y RNA homolog. Total RNA from embryo, each larval stage worms and adult worms were blotted onto the membrane. The results were compared with the FISH experiment data. In most cases, the results of northern hybridization and FISH were consistently elucidated. Intriguingly, two bands of different size in northern hybridization were detected with the Cel-7 antisense oligo DNA probe. The RNAs were designated as Cel-7l (longer one) and Cel-7s (shorter one). Cel-7l increased as the developmental stage of worms proceeded but Cel-7s was detected most in embryo and adult. In addition, Cel-7s decreased in two different rop-1 mutants, but Cel-7l was not affected by the decrease of ROP-1. These indicated that Cel-7l RNA and Cel-7s RNA have alternative functions.

Ken-ichi Oshio et al. (2002) Japanese Worm Meeting "Revision of synaptic connectivity database"

Eizo Akiyama, Yuishi Iwasaki, Yuko Osana, Ken-ichi Oshio, Sohei Gomi, Satoru Morita, Kotaro Oka, Kazumi Omata

[Japanese Worm Meeting, 2002]

The synaptic connectivity of C. elegans is well known from observations of the somatic system by White et al. and those of the pharyngeal system by Albertson et al. So far, three databases were constructed for computational usage by Achacoso et al. and Durbin, and recently in WormBase. However, they lack some data such as those in tables of White's paper and those in figures of Albertson's book. Our database (K. Oshio, S. Morita, Y. Osana and K. Oka: Technical Report of CCEP, Keio Future No.1, 1998) includes all data described in White's paper and Albertson's book. Unfortunately, some mistakes were found in the database through private communications with John White who is the author of White's paper and with the users of the database. Thus we have been proceeding with the revision to make it perfect one. We are planning to complete the revision in September 2002. The database should be worthwhile not only for neurophysiological studies, but also for post-genomic interests mediating genomes and behavior.