Meng L et al. (2020) Dev Cell "NLR-1/CASPR Anchors F-Actin to Promote Gap Junction Formation."

Yan D, Meng L

[Dev Cell, 2020]

Gap junctions are present in most tissues and play essential roles in various biological processes. However, we know surprisingly little about the molecular mechanisms underlying gap junction formation. Here, we uncover the essential role of a conserved EGF- and laminin-G-domain-containing protein nlr-1/CASPR in the regulation of gap junction formation in multiple tissues across different developmental stages in C.elegans. NLR-1 is located in the gap junction perinexus, a region adjacent to but not overlapping with gap junctions, and forms puncta before the clusters of gap junction channels appear on the membrane. We show that NLR-1 can directly bind to actin to recruit F-actin networks at the gap junction formation plaque, and the formation of F-actin patches plays a critical role in the assembly of gap junction channels. Our findings demonstrate that nlr-1/CASPR acts as an early stage signal for gap junction formation through anchoring of F-actin networks.

Meng L et al. (2016) Elife "Regulation of Neuronal Axon Specification by Glia-Neuron Gap Junctions in C. elegans."

Meng L, Jin Y, Zhang A, Yan D

[Elife, 2016]

Axon specification is a critical step in neuronal development, and the function of glial cells in this process is not fully understood. Here we show that C. elegans GLR glial cells regulate axon specification of their nearby GABAergic RME neurons through GLR-RME gap junctions. Disruption of GLR-RME gap junctions causes misaccumulation of axonal markers in non-axonal neurites of RME neurons and converts microtubules in those neurites to form an axon-like assembly. We further uncover that GLR-RME gap junctions regulate RME axon specification through activation of the CDK-5 pathway in a calcium-dependent manner, involving a calpain clp-4. Therefore, our study reveals the function of glia-neuron gap junctions in neuronal axon specification and shows that calcium originated from glial cells can regulate neuronal intracellular pathways through gap junctions.

Meng L et al. (2016) PLoS Genet "Regulation of Gap Junction Dynamics by UNC-44/ankyrin and UNC-33/CRMP through VAB-8 in C. elegans Neurons."

Chen CH, Meng L, Yan D

[PLoS Genet, 2016]

Gap junctions are present in both vertebrates and invertebrates from nematodes to mammals. Although the importance of gap junctions has been documented in many biological processes, the molecular mechanisms underlying gap junction dynamics remain unclear. Here, using the C. elegans PLM neurons as a model, we show that UNC-44/ankyrin acts upstream of UNC-33/CRMP in regulation of a potential kinesin VAB-8 to control gap junction dynamics, and loss-of-function in the UNC-44/UNC-33/VAB-8 pathway suppresses the turnover of gap junction channels. Therefore, we first show a signal pathway including ankyrin, CRMP, and kinesin in regulating gap junctions.

Meng L et al. (2015) Cell Rep "The Cell Death Pathway Regulates Synapse Elimination through Cleavage of Gelsolin in Caenorhabditis elegans Neurons."

Cook SJ, Yan D, Meng L, Mulcahy B, Neubauer M, Wan A, Jin Y

[Cell Rep, 2015]

Synapse elimination occurs in development, plasticity, and disease. Although the importance of synapse elimination has been documented in many studies, the molecular mechanisms underlying this process are unclear. Here, using the development of C. elegans RME neurons as a model, we have uncovered a function for the apoptosis pathway in synapse elimination. We find that the conserved apoptotic cell death (CED) pathway and axonal mitochondria are required for the elimination of transiently formed clusters of presynaptic components in RME neurons. This function of the CED pathway involves the activation of the actin-filament-severing protein, GSNL-1. Furthermore, we show that caspase CED-3 cleaves GSNL-1 at a conserved C-terminal region and that the cleaved active form of GSNL-1 promotes its actin-severing ability. Our data suggest that activation of the CED pathway contributes to selective elimination of synapses through disassembly of the actin filament network.

Forrester S et al. (2007) Foodborne Pathog Dis "Evaluation of the pathogenicity of Listeria spp. in Caenorhabditis elegans."

Schwab U, Wiedmann M, Hoose WA, Milillo SR, Forrester S

[Foodborne Pathog Dis, 2007]

Caenorhabditis has proven to be a useful model for studying host-pathogen interactions as well as the ability of nematodes to serve as vectors for the dispersal of foodborne pathogens. In this study, we evaluated whether C. elegans can serve as a host for Listeria spp. While there was an effect of growth media on C. elegans killing, C. elegans exposed to L. monocytogenes and L. innocua pregrown in Luria-Bertani medium showed reduced survival when compared to nonpathogenic E. coli OP50, while L. seeligeri showed survival similar to E. coli OP50. In a preference assay, C. elegans preferred E. coli over L. monocytogenes and L. innocua, but showed no preference between L. monocytogenes and L. innocua. A gentamicin assay indicated that L. monocytogenes did not persist within the C. elegans intestinal tract. Our findings that L. monocytogenes and L. innocua strains tested have equally deleterious effects on C. elegans and that L. monocytogenes did not establish intestinal infection conflict with other recently published results, which found intestinal infection and killing of C. elegans by L. monocytogenes. Further studies are thus needed to clarify the interactions between L. monocytogenes and C. elegans, including effects of environmental conditions and strain differences on killing and intestinal infection.

Abraham D et al. (1989) Am J Trop Med Hyg "Immunity to larval Brugia malayi in BALB/c mice: protective immunity and inhibition of larval development."

Grieve RB, Christensen BM, Abraham D, Holy JM

[Am J Trop Med Hyg, 1989]

The objective of this study was to analyze the immune response of mice to the larval stages of Brugia malayi. Male BALB/c mice were inoculated with 3 doses of irradiated third-stage larvae (L-3) of B. malayi and were subsequently challenged with L-3 implanted ip within diffusion chambers. After 3 weeks, larvae were recovered to determine their viability, length, and stage of development. A significant reduction in parasite survival was observed in immunized mice. Furthermore, larvae recovered from immunized mice were significantly shorter than larvae recovered from control mice. All larvae recovered from immunized mice were L-3, whereas 96% of larvae recovered from controls were fourth-stage larvae (L-4). Sera collected from control and immunized mice were tested for the presence of antibodies reactive with L-3 and L-4 antigens using an indirect fluorescent antibody assay employing frozen larval cross-sections as antigen. Sera recovered after challenge of control mice reacted with internal, but not surface, antigens of L-3 and L-4. Alternatively, sera from immunized mice reacted with both internal and external antigens of both L-3 and L-4.

Sese BT et al. (2009) J Toxicol Environ Health A "Toxicity of polycyclic aromatic hydrocarbons to the nematode Caenorhabditis elegans."

Reid BJ, Grant A, Sese BT

[J Toxicol Environ Health A, 2009]

The presence of polycyclic aromatic hydrocarbons (PAHs) in the environment has attracted much concern owing to their mutagenic and carcinogenic properties. Regulatory authorities have favored the use of biological indicators as an essential means of assessing potential toxicity of environmental pollutants. This study aimed to assess the toxicity of acenaphthene, phenanthrene, anthracene, fluoranthene, pyrene, and benzo[a]pyrene to Caenorhabditis elegans by measuring LC50 and EC50 values for growth and reproduction. The exposure to all chemicals was carried out in aqueous medium. All PAHs showed a low acute toxicity to C. elegans. There was no significant mortality in C. elegans after 24 h of exposure at PAH concentrations within (and indeed above) their respective solubility limits. Prolonged exposure (72 h) at high concentrations for acenaphthene (70,573 microg/L), phenanthrene (3758 microg/L), anthracene (1600 microg/L), fluoranthene (1955 microg/L), pyrene (1653 microg/L), and benzo[a]pyrene (80 microg/L) produced mortality. Results also showed that reproduction and growth were much more sensitive parameters of adverse response than lethality, and consequently may be more useful in assessing PAH toxicity using C. elegans. In comparison with previous studies, C. elegans was found to be approximately 2-fold less sensitive to acenaphthene, 5-fold less sensitive to phenanthrene, and 20-fold less sensitive to fluoranthene than Daphnia magna. However, the 48-h LC50 for benzo[a]pyrene (174 microg/L) reported in the present study with C. elegans was similar to that reported elsewhere for Daphnia magna (200 microg/L). Although C. elegans indicated greater sensitivity to benzo[a]pyrene than Artemia salina (174 microg/L vs. 10000 microg/L), the organism showed less sensitivity to pyrene (8 microg/L vs. 2418 microg/L), fluoranthene (40 microg/L vs. 2719 microg/L), and phenanthrene (677 microg/L vs. 4772 microg/L) than Artemia salina. Caenorhabditis elegans, while not the most sensitive of species for PAH toxicity assessment, may still hold applicability in screening of contaminated soils and sediments.

Manalo RVM et al. (2020) Pharm Biol "Caffeine reduces deficits in mechanosensation and locomotion induced by L-DOPA and protects dopaminergic neurons in a transgenic Caenorhabditis elegans model of Parkinson's disease."

Medina PMB, Manalo RVM

[Pharm Biol, 2020]

CONTEXT: L-DOPA is the first-line drug for Parkinson's disease (PD). However, chronic use can lead to dyskinesia. Caffeine, which is a known neuroprotectant, can potentially act as an adjunct to minimise adverse effects of L-DOPA. OBJECTIVES: (Rhabditidae) strain UA57 overexpressing tyrosine hydroxylase (CAT-2) when treated with caffeine, L-DOPA or their combinations. MATERIALS AND METHODS: =20). Meanwhile, mechanosensation and locomotion under vehicle (0.1% DMSO), L-DOPA (60mM), caffeine (10mM) or 60mM L-DOPA + 10 or 20mM caffeine (60LC10 and 60LC20) treatments were scored for 3days. RESULTS: Taken together, we show that caffeine can protect DAergic neurons and can reduce aberrant locomotion and loss of sensation when co-administered with L-DOPA, which can potentially impact PD treatment and warrants further investigation.

Buyannemekh K et al. (2024) Dev Biol "Left/right asymmetrically expressed ephrin and Flamingo proteins regulate lateralized axon growth in C. elegans."

Buyannemekh K, Bertrand V, Villoutreix P

[Dev Biol, 2024]

While the nervous system of bilaterian animals is mainly left-right (L-R) symmetric at the anatomical level, some molecular and functional L-R asymmetries exist. However, the extent of these molecular asymmetries and their functional consequences remain poorly characterized. C. elegans allows to study L-R asymmetries in the nervous system with single-neuron resolution. We have previously shown that a neural bHLH transcription factor, HLH-16/Olig, is L-R asymmetrically expressed in the AIY neuron lineage and regulates AIY axon projections in a L-R asymmetric manner. Here, by combining a candidate approach and single-cell RNA sequencing data analysis, we identify the ephrin protein EFN-2 and the Flamingo protein FMI-1 as downstream targets of HLH-16 that are L-R asymmetrically expressed in the AIY lineage. We show that EFN-2 and FMI-1 collaborate in the L-R asymmetric regulation of axonal growth. EFN-2 may act via a non-canonical receptor of the L1CAM family, SAX-7. Our study reveals novel molecular L-R asymmetries in the C. elegans nervous system and their functional consequences.

Pohl C (2011) Commun Integr Biol "Left-right patterning in the C. elegans embryo: Unique mechanisms and common principles."

Pohl C

[Commun Integr Biol, 2011]

The development of bilateral symmetry during the evolution of species probably 600 million years ago brought about several important innovations: It fostered efficient locomotion, streamlining and favored the development of a central nervous system through cephalization. However, to increase their functional capacities, many organisms exhibit chirality by breaking their superficial left-right (l-r) symmetry, which manifests in the lateralization of the nervous system or the l-r asymmetry of internal organs. In most bilateria, the mechanisms that maintain consistent l-r asymmetry throughout development are poorly understood. This review highlights insights into mechanisms that couple early embryonic l-r symmetry breaking to subsequent l-r patterning in the roundworm Caenorhabditis elegans. A recently identified strategy for l-r patterning in the early C. elegans embryo is discussed, the spatial separation of midline and anteroposterior axis, which relies on a rotational cellular rearrangement and non-canonical Wnt signaling. Evidence for a general relevance of rotational/torsional rearrangements during organismal l-r patterning and for non-canonical Wnt signaling/planar cell polarity as a common signaling mechanism to maintain l-r asymmetry is presented.