Liu, Zheng et al. (2015) International Worm Meeting "A redundant neural circuit drives C. elegans responses to social cues."

Tong, Ada, Leinwand, Sarah, Curran, Kevin, Chalasani, Sreekanth, Chute, Christopher, Liu, Zheng, Srinivasan, Jagan

[International Worm Meeting, 2015]

Animals communicate with each other using social cues. Typically, the sender sends a signal that modifies the current and/or future behaviors of the receiver. One particular form of communication that has been well studied is the interactions between a predator (sender) and prey (receiver). Despite these efforts, the neural circuits in the receiver that detect signals and driving behaviors remain poorly understood. We have developed a novel model of social behaviors analyzing the interactions between two nematodes P. pacificus (sender) and C. elegans (receiver).We find that C. elegans avoids secretions from a starving P. pacificus. We used cell ablations and calcium imaging to map the underlying sensory circuit. We find that either ASH and ASI or ASH and ASJ neurons detect P. pacificus derived signals. Moreover, we show that tax-4 (cyclic nucleotide gated ion channel) is required in both ASI and ASJ neurons while ocr-2 (TRP channel) is required in ASH for the avoidance response. We performed a pilot screen using small molecule drugs and identified Sertraline, (Zoloft, a selective serotonin reuptake inhibitor) as a candidate hit. Animals treated with Zoloft show greatly attenuated responses to P. pacificus. Surprisingly, its action requires GABA but not serotonin signaling to attenuate C. elegans avoidance. Apart from this rapid avoidance, we also show that prolonged exposure to Pristionchus secretions also modifies future C. elegans behaviors. These studies show how a receiver neural circuit detects social signals and modifies its current and future behaviors. .

Zheng Liu et al. (2006) Development & Evolution Meeting "The chromodomain protein MRG-1 is required for germline development in C. elegans"

Hiroshi Sakamoto, Zheng Liu, Susan Strome, Teruaki Takasaki

[Development & Evolution Meeting, 2006]

Germ cells are considered to be immortal and totipotent. In order to preserve those traits, germ cells must be set apart from the soma and must employ special protective mechanisms. One mechanism used is chromatin-level repression. C. elegans MRG-1 appears to be involved in such chromatin-level repression. MRG-1 is a chromodomain-containing protein that is present in germ cells at all stages of development. We obtained three mrg-1 deletion alleles, all of which appear to be null alleles. Mutations in mrg-1 cause maternal-effect sterility in both hermaphrodites and males. Zygotic expression of MRG-1 can rescue fertility, at low frequency in hermaphrodites and at high frequency in males. The mrg-1/mrg-1 offspring of mrg-1/+ mothers are fertile but display desilencing of transgenes in repetitive extrachromosomal arrays. Their offspring are sterile due to failure in germline proliferation. Most of these phenotypes are shared with the mes mutants. Interestingly, in early embryos GFP::MRG-1 (driven by the pie-1 promoter) is concentrated on the 5 autosomes in each pronucleus, similar to MES-4. Our studies of MRG-1 suggest that it is maternally required for proper proliferation of the primordial germ cells in larvae and for fertility. Transgene analysis in worms and the known roles of chromodomain proteins in other organisms suggest that MRG-1may function to regulate chromatin organization and gene expression patterns. The similar autosomal concentration of MRG-1 and the histone methyltransferase MES-4 and the fact that chromodomains are known to bind methylated histone tails raise the exciting possibility that MRG-1 is a downstream effector of MES-4 in regulation of chromatin in the germ line.

Liu J et al. (2024) STAR Protoc "Protocol for survival assay of Caenorhabditis elegans to Pseudomonas aeruginosa PA14 infection."

Wang M, Liu J, Lei M, Tu H, Chen S

[STAR Protoc, 2024]

The nematode Caenorhabditis elegans is a powerful model organism for studying the molecular and cellular mechanisms of innate immunity governed by the intestine. Here, we present a protocol to perform C. elegans survival assays to infection by the bacterial pathogen Pseudomonas aeruginosa PA14. Specifically, we describe steps for preparing C. elegans strains and PA14 bacteria for survival assays. This protocol will assist researchers to study genes involved in intestinal innate immunity and gut defense against pathogen infection. For complete details on the use and execution of this protocol, please refer to Liu et al.¹ and Zheng et al.².

Kaplan HS et al. (2018) Neuron "Sensorimotor Integration for Decision Making: How the Worm Steers."

Zimmer M, Kaplan HS

[Neuron, 2018]

Animals' movements actively shape their perception and subsequent decision making. In this issue of Neuron, Liu etal. (2018) show how C.elegans nematodes steer toward an odorant: a dedicated interneuron class integrates oscillatory olfactory signals, generated by head swings, with corollary discharge motor signals.

Ali L et al. (2020) J Cell Biol "Mitochondrial translation, dynamics, and lysosomes combine to extend lifespan."

Ali L, Haynes CM

[J Cell Biol, 2020]

In this issue, Liu et al. (2019. J. Cell. Biol.https://doi.org/10.1083/jcb.201907067) find that the inhibition of mitochondrial ribosomes in combination with impaired mitochondrial fission or fusion increases C. elegans lifespan by activating the transcription factor HLH-30, which promotes lysosomal biogenesis.

Philippidou P et al. (2015) Neuron "Sensory-Motor Circuits: Hox Genes Get in Touch."

Philippidou P, Dasen JS

[Neuron, 2015]

Sensory-motor reflex circuits are the basic units from which animal nervous systems are constructed, yet little is known regarding how connections within these simple networks are established. In papers in Cell Reports and in this issue of Neuron, Zheng et al. (2015a, 2015b) demonstrate that coordinate activities of Hox genes in sensory neurons and interneurons govern connectivity within touch-reflex circuits in C. elegans.

Rahmani, Shapour et al. (2021) MicroPubl Biol

Tuck, Simon, Rahmani, Shapour

[MicroPubl Biol, 2021]

C. elegans males that have come into close proximity of hermaphrodites initiate copulatory behavior comprising at least five different steps termed response, turning, location of vulva, spicule insertion and sperm transfer (Loer and Kenyon 1993, Liu and Sternberg 1995, Chute and Srinivasan 2014). Mutations specifically affecting different steps have been isolated and characterized (Barr and Sternberg 1999, Hajdu-Cronin et al. 2017, Liu et al. 2017). However, our understanding of the molecular mechanisms acting in the neurons controlling copulation is far from complete. During the response step, males that have sensed the presence of a hermaphrodite move backwards in such a way that the males tail fan glides along the surface of the hermaphrodite until the tail reaches the vulva (or head or tail) (Loer and Kenyon 1993, Liu and Sternberg 1995, Sherlekar and Lints 2014). Response behavior is regulated by ciliated neurons in the tail whose dendrites lie in sensory rays within the fan (Liu and Sternberg 1995). If a male reaches the end of the hermaphrodite without having found the vulva, it executes a turn during which the tail bends tightly ventrally so that contact is established between the ventral surface of the fan and the other side of the intended mate (Loer and Kenyon 1993, Liu and Sternberg 1995). The ability to execute turns efficiently is dependent upon serotonergic neurons in the posterior ventral nerve cord (the CP neurons) and on their ability to produce serotonin (Loer and Kenyon 1993, Carnell et al. 2005). Serotonin stimulates the diagonal muscles in the tail to induce curling ventrally by stimulating a serotonin receptor, SER-1 (Loer and Kenyon 1993, Carnell et al. 2005). However, how serotonin affects diagonal muscles and ventral turning is not fully understood.

Kirkwood TB (2013) Cell Metab "Untangling functional declines in the locomotion of aging worms."

Kirkwood TB

[Cell Metab, 2013]

All physiological functions decline with age, but which changes are primary and which are secondary is not always clear. Liu et al. (2013), examining functional changes in the muscles and motor neurons of C. elegans, suggest that when it comes to locomotion, it is the nervous system that shows earlier age-related deterioration.

Rui Wang et al. (2005) International Worm Meeting "Identifying genes required for the function of glutamatergic synapses"

Rui Wang, Andres Maricq, Yi Zheng, Penelope Brockie

[International Worm Meeting, 2005]

Glutamatergic neurotransmission accounts for the vast majority of excitatory synaptic signaling in the vertebrate central nervous system. An important problem in neurobiology is to understand how glutamatergic synapses are formed and regulated. Recently, molecules required for activity of ionotropic glutamate receptors (iGluRs) have been identified, shedding more light on the mechanisms underlying the regulation of iGluRs. However, we still have much to learn regarding how iGluRs are synthesized, assembled, localized to the surface of appropriate synapses, and how receptor function is regulated once at the synapse. To address these questions, we have undertaken a genetic screen for modifiers of a dominantly active variant of the GLR-1 iGluR subunit in C. elegans. GLR-1 is expressed in many neurons, including the command interneurons that control locomotion. Introducing an alanine (A) to threonine (T) mutation in a highly conserved site of GLR-1 causes transgenic lurcher worms that express the GLR-1(A/T) variant to rapidly switch between forward and backward movement (Zheng et al., 1999). This dramatic phenotype provided a tool used in a suppressor screen to identify genes required for GLR-1 function. Thus, the sol-1 (suppressor of lurcher) gene was isolated (Zheng et al., 2004). In an attempt to enhance the suppressor screen, we have engineered a second mutation, glutamine (Q) to tyrosine (Y), in the GLR-1(A/T) variant. The GLR-1(Q/Y) mutation inhibits receptor desensitization (Brockie et al., 2001). Transgenic worms that express GLR-1(Q/Y; A/T) have a super-lurcher phenotype, switching between forward and backward movement at a higher frequency than transgenic GLR-1(A/T) worms. We have also tagged GLR-1(Q/Y; A/T) with GFP to facilitate the characterization of genes identified in the suppressor screen. We have screened approximately 15,000 mutagenized GLR-1 (A/T; Q/Y) haploid genomes and isolated 5 candidate suppressors of the super-lurcher locomotion phenotype. We are currently mapping and cloning these genes. Brockie et al. (2001) Neuron 31: 617-30 Zheng et al. (1999) Neuron 24: 347-61 Zheng et al. (2004) Nature 427: 451-7

Kundu ST et al. (2010) J Biol "Robust and specific inhibition of microRNAs in Caenorhabditis elegans."

Slack FJ, Kundu ST

[J Biol, 2010]

MicroRNAs (miRNAs) are small non-coding RNAs that regulate the expression of numerous target genes. Yet, while hundreds of miRNAs have been identified, little is known about their functions. In a recent report published in Silence, Zheng and colleagues demonstrate a technique for robust and specific knockdown of miRNA expression in Caenorhabditis elegans using modified antisense oligonucleotides, which could be utilized as a powerful tool for the study of regulation and function of miRNAs in vivo.