Anita Sicilia et al. (2002) European Worm Meeting "Characterization of Neuropeptide Receptors in Caenorhabditis elegans."

Lindy Holden-Dye, Anita Sicilia, Chris Keating, Neville Ashcroft, Maggie Daniels, Julian Burke

[European Worm Meeting, 2002]

Neuropeptides are classical neurotransmitters that also act as neuromodulators. The family of peptides most studied in C. elegans is the FMRFamide-like peptides encoded by flp genes. Little is known of their function although it is thought they have a role in locomotion, egg laying and pharyngeal pumping. The aim of this project is to characterize neuropeptide signalling and identify their receptors.

Yuishi Iwasaki (2005) International Worm Meeting "How to model and study a partial neural circuit of C. elegans?"

Yuishi Iwasaki

[International Worm Meeting, 2005]

In a numerical study of a partial neural circuit for a certain behavior, there are two general problems. (i) To simulate a certain behavior of a worm, we usually adopt only the neurons which are mainly associated with its behavior. The influence of the remaining neurons of C. elegans is completely neglected (closed circuit). However, the behavior is realized by the whole neural circuit with an external stimulation (open circuit). There is no guarantee that a numerical result in the closed partial neural circuit is consistent with that in the open circuit. This is a problem in neural modeling. (ii) To assign a behavioral criterion to the neural circuit, we usually analyze a stationary state of the neuron. That is, all the membrane potentials Vi(t) are dVi(t)/dt=0 in the neural circuit. However, it is not clear that the neuron is in a stationary state or not when a worm is moving. This is a problem in analyzing the neural circuit.To solve the former problem (i), a mathematical formulation has been proposed for the McCulloch-Pitts model (Iwasaki, Y. and Gomi, S. (2004). Bulletin of Mathematical Biology, 66, 727-743). The influence of the remaining neurons on the associated neurons is formulated as the external noise for a partial neural circuit. Since the neural connectivity of C. elegans has been completely determined, the stochastic property of the external noise is appropriately evaluated by the neural connectivity. Thus the degree of freedom is effectively reduced in neural modeling. However, the McCulloch-Pitts model is not the most suitable model to represent a real nervous system of C. elegans since the McCulloch-Pitts neuron is activated stepwisely. In this presentation, a mathematical formulation for a more physiologically adequate neural model is proposed. Furthermore, this formulation is applied to behavioral neural circuits of C. elegans. Considering the latter problem (ii), the dynamics of the neural circuit is analyzed. This work was supported by JSPS (No. RFTF-96I00102) and MEXT (No. 16740239).

Jesse Gray et al. (2002) West Coast Worm Meeting "Dissecting the Neural Circuit Controlling Chemotaxis in C. elegans"

Jesse Gray, Cori Bargmann

[West Coast Worm Meeting, 2002]

The behavior of humans and other animals is generated by neural circuits. Elucidating the logic of information processing in circuits is an important step in understanding how behavior is generated. We are studying the C. elegans chemotaxis circuit, a simple circuit that nevertheless carries out complex behaviors.

Wieringa B et al. (2000) West Coast Worm Meeting "Unraveling the biological role of DMWD, a gene close to the unstable CTG-repeat in the myotonic dystrophy locus."

Wieringa B, Mains PE, Westerlaken J

[West Coast Worm Meeting, 2000]

Myotonic Dystrophy (DM) is a frequent autosomal dominant disorder, caused by the expansion of an unstable (CTG)n-repeat. The expanding repeat is located in the 3'-untranslated region of the DM protein kinase gene (DMPK). The DMPKgene is located in a gene dense area, therefore it is unclear if it is theonly gene involved in disease manifestation. Another possible candidate is the DMWD gene (formally known as DMR-N9 in mouse, or gene 59 in human), which is located closely upstream of the DMPK gene. The DMWD gene is mainly expressed in brain, testis and some smooth muscle tissues. In brain the protein is located in many areas, but most prominently in places where there are synaptic glomeruli. In testis the protein appears to be located in several distinct stages of spermatogenesis. The DMWD gene is conserved during evolution and has homologs in plant, yeast and nematodes. To futher understand the biological role of DMWD we started to investigate the C. elegans DMWD gene. In C. elegans DMWD RNA is expressed in embryos and gravid adults. Preliminary results from RNAi studies suggest that some progeny of the injected worms are sterile. We are further planning to do RNA in situ hybridisation, GFP tagging of the protein and antibody staining experiments.

Kotaro Oka et al. (2003) International Worm Meeting "Neuronal Circuit and Native Responses of C. elegans"

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

[International Worm Meeting, 2003]

The ultimate goal of the present work is to determine pathways of neuronal signal from sensory neurons to motoneurons in occasion of native responses of C. elegans. The fundamental hypothesis is that the pathways consists of highly multiple synaptic connection among interneurons. The McCulloch-Pitts equation is employed to find out sequence of much synaptic connection from each sensory neuron. Although the McCulloch-Pitts equation cannot be used for simulation of propagation of neuronal signal without knowledge about physical parameters within it, it is useful for the present purpose. The point of the algorithm is ; (i) threshold of menbrain potential is replaced by an integer s which is independent of the neuron and (ii) the coupling coefficient between a pair of neurons is replaced with number of synapses between them. When a sensory neuron is always excited, a stationary distribution of excited neurons is realized. Excited neurons in the stationary state are connected to the sensory neuron by pathways which consist of synaptic connection of multiplicity larger than s. A neuron, which is connected with more than one excited neurons, is also excited when the sum of multiplicity of joined synapses are larger than s. A plan of the neuronal circuit is constructed from neurons, which are excited for s more than six, and synapses connecting them. Interneurons are classified into three groups. Three elementary motions of the worm are defined in terms of motoneurons which are simultaneously excited and its behavior in occasion of native responses is combination of such elementary motions. The number of synapses have been counted using the database constructed by our research group. It is translation from the sketch of neurons published by White et al.. into a digital form.

Marc Hammarlund et al. (2006) Neuronal Development, Synaptic Function, and Behavior Meeting "Neurons that Lack beta;-Spectrin Break and Degenerate"

Marc Hammarlund, Michael Bastiani, Erik Jorgensen

[Neuronal Development, Synaptic Function, and Behavior Meeting, 2006]

beta;-spectrin is highly expressed in developing neurons, and loss of the protein results in defects in axon structure. These data suggest that spectrin could be required for axon extension during development. Here, we demonstrate that beta;-spectrin is not required for axon outgrowth in the nematode C. elegans, but is rather required for resistance of axons to mechanical stress. Axons form normally in beta;-spectrin mutants. However, as these animals age, spontaneous axotomy initiates degeneration of the nervous system. Degeneration is rescued by preventing movement, demonstrating that axon breakage is caused by acute mechanical stress. Longitudinal studies show that after breaking, axons initiate regrowth, which often fails. Detached fragments are removed by Wallerian degeneration, and this process is blocked by overexpressing nicotinamide mononucleotide adenylyltransferase (Nmnat). Removal of the fragments also requires the engulfment protein CED-1. Our results demonstrate that beta;-spectrin is required for neuronal elasticity. Since spectrin is a major target of calpain proteolysis, it is possible that some neurodegenerative disorders may arise from cleavage of spectrin followed by axon breakage.

Kimura, Yoshishige et al. (2013) International Worm Meeting "Starvation-responsive behavioral plasticity is tuned by tubulin polyglutamylation in sensory cilia."

Konno, Alu, Tsutsumi, Koji, Kimura, Yoshishige, Setou, Mitsutoshi, Hameed, Saira

[International Worm Meeting, 2013]

Caenorhabditis elegans shows various well-characterized sensory behaviors. We have identified that an osmotic avoidance was partially suppressed by starvation, that is dependent on ttll-4 gene encoding a tubulin glutamate-ligase essential for tubulin polyglutamylation of axonemal microtubules (MTs) in sensory cilia. Tubulin polyglutamylation is a post-translational modification (PTM) that generates lateral glutamate chains on target proteins, and changes the interaction between MT and associated proteins. Measurement of the velocity of intraflagellar transport (IFT) particles has revealed that starvation accelerates IFT, which is also dependent on the level of tubulin modification. Additionally, ttll-4 is activated under the control of p38 MAPK. Tubulin polyglutamylation level in sensory cilia is also enhanced by various environmental stimuli including starvation. Amino acid substitution of TTLL-4 has specified a threonine residue, which is a putative MAPK-phosphorylation site, is required for enhancement of both IFT and tubulin polyglutamylation. Similar elevation of tubulin polyglutamylation is also observed in mammalian photoreceptor cells in retina responding to light exposure. These results indicate that environmental responsiveness of tubulin polyglutamylation in cilia is regulated by evolutionary-conserved molecular mechanism.

Tugba Guven et al. (2005) International Worm Meeting "A screen for regulators of egl-1 expression"

Malia Potts, Tugba Guven, Scott Cameron

[International Worm Meeting, 2005]

BH3 domain encoding gene egl-1 is the most upstream gene in the programmed cell death pathway, and is essential for death of essentially all somatic cells. While a great deal is known about how programmed cell death is executed, less is known about how this fate is determined during development and the knowledge about the cell-specific regulators of egl-1 is limited. In some cells, regulation of egl-1 transcription is critical. For example, in the HSN neurons of hermaphrodites the transcription factor TRA-1 directly represses egl-1 expression and programmed cell death. Similarly, in specific cells of the pharynx the ces-2 and ces-1 genes regulate egl-1 transcription to ensure death of cells; in this process CES-1 competes with the HLH-2 and HLH-3 proteins as direct regulators of egl-1. Our aim is to elucidate other cell-specific regulators of egl-1 expression. We plan to screen transgenic animals carrying a Pegl-1gfp reporter plasmid for abnormal patterns of egl-1 expression using mutagenesis, and will present our progress.

Kyung Min Ko et al. (2005) International Worm Meeting "Isolation and Characterization of deletion mutant of inorganic pyrophosphatase in C.elegans."

Joohong Ahnn, Kyung Min Ko

[International Worm Meeting, 2005]

Hydrolysis of inorganic pyrophosphate is catalyzed by an enzyme inorganic pyrophosphatase (PPase). It has been suggested that catalysis of PPase is the thermodynamic driving force for a number of important biosynthetic reactions. The enzyme is also shown to be essential for viability of yeast and bacteria. Comparative proteomics studies have been shown that the level of PPase is significantly altered in samples of gastric cancer patients. The C. elegans genome database revealed the presence of a predicted PPase gene (ppa-1) which is located on cosmid C47E12.4 (LGIV). It shows about 54% amino acid identity with human PPase. The ppa-1 is strongly expressed in the intestine. Recombinantly expressed enzyme exhibits specific activity of catalyzing hydrolysis of PPi to Pi in vitro. The deletion mutant revealed developmental arrest phenotype at L2 stage, which suggests that ppa-1 is essential for larval development. In addition, the deletion mutant showed developmental defects of intestine, suggesting that ppa-1 is important for intestinal development in C. elegans.

Michelle Rengarajan et al. (2002) West Coast Worm Meeting "Infection of Drosophila melanogaster with Heterorhabditis bacteriophora"

Takao Inoue, Michelle Rengarajan, Paul W Sternberg

[West Coast Worm Meeting, 2002]

Heterorhabditis bacteriophora is a parasitic nematode capable of infecting a wide variety of insects. The infectious juvenile (IJ, equivalent to the C. elegans dauer) harbors symbiotic bacterium Photorhabdus luminescens, which is used to kill the host. This is a potentially useful system for studying of bacteria/nematode symbiosis, bacteria/insect pathogenesis and nematode/insect parasitism.