Elegans wnt

Vanilloids, including capsaicin and eugenol, are ligands of transient receptor potential channel vanilloid subfamily member 1 (TRPV1). Prolonged treatment with vanilloids triggered the desensitization of TRPV1, leading to analgesic or antinociceptive effects. Caenorhabditis elegans (C. elegans) is a model organism expressing vanilloid receptor orthologs (e.g., OSM-9 and OCR-2) that are associated with behavioral and physiological processes, including sensory transduction. We have shown that capsaicin and eugenol hamper the nocifensive response to noxious heat in C...

The Developmental Origins of Health and Disease (DOHaD) hypothesis postulates that early-life stressors can predispose people to disease later in life. In the roundworm Caenorhabditis elegans, prolonged early-life starvation causes germline tumors, uterine masses and other gonad abnormalities to develop in well-fed adults. Reduction of insulin/insulin-like growth factor (IGF) signaling (IIS) during larval development suppresses these starvation-induced abnormalities. However, molecular mechanisms at play in formation and suppression of starvation-induced abnormalities are unclear...

Precise synaptic connection of neurons with their targets is essential for the proper functioning of the nervous system. A plethora of signaling pathways act in concert to mediate the precise spatial arrangement of synaptic connections. Here we show a novel role for a gap junction protein in controlling tiled synaptic arrangement in the GABAergic motor neurons in Caenorhabditis elegans , in which their axons and synapses overlap minimally with their neighboring neurons within the same class. We found that while EGL-20/Wnt controls axonal tiling, their presynaptic tiling is mediated by a gap junction protein UNC-9/Innexin, that is localized at the presynaptic tiling border between neighboring dorsal D-type GABAergic motor neurons...

Alterations in the intestinal physiology caused by pathogen colonization result in immune activation. To provide insights into the mechanisms underlying the control of immune activation by changes in intestinal homeostasis, we conducted a forward genetic screen for suppressors of immune activation by intestinal distension in Caenorhabditis elegans. Our results indicate that C. elegans ACC-4, a member of a family of acetylcholine receptors, is required in immune activation by defects in the defecation motor program or by pathogen infection...

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Transdifferentiation, or direct cell reprogramming, is the conversion of one fully differentiated cell type into another. Whether core mechanisms are shared between natural transdifferentiation events when occurring with or without cell division is unclear. We have previously characterized the Y-to-PDA natural transdifferentiation in Caenorhabditis elegans, which occurs without cell division and requires orthologs of vertebrate reprogramming factors. Here, we identify a rectal-to-GABAergic transdifferentiation and show that cell division is required but not sufficient for conversion...

In the clinical intensive care units (ICU), the traditional Chinese medicine (TCM) formulation of Xuebijing has been frequently used for treating sepsis. Nevertheless, the underlying pharmacological mechanisms of Xuebijing remain largely unclear. Caenorhabditis elegans is an important experimental host for bacterial infections. Using C. elegans as an animal model, we here examined the potential of Xuebijing treatment against bacterial infection and the underlying mechanisms. Xuebijing treatment could inhibit the reduction tendency of lifespan caused by Pseudomonas aeruginosa infection...

Polystyrene nanoparticles (PS-NPs) have a potential toxicity on offspring after the exposure. However, the molecular basis for PS-NP in inducing transgenerational toxicity remains largely unknown. In this study, the role and the underlying mechanism of germline Wnt signaling in regulating transgenerational toxicity of PS-NPs were determined using an in vivo animal model of Caenorhabditis elegans. Exposure to PS-NP (1-100 μg/L) increased expression of Wnt ligand LIN-44 and decreased expression of Wnt receptor MIG-1...

Neurodegenerative diseases (NDs) such as Alzheimer's disease, Parkinson's disease, and Huntington's disease are incurable diseases with progressive loss of neural function and require urgent development of effective treatments. Carnosol (CL) reportedly has a pharmacological effect in the prevention of dementia. Nevertheless, the mechanisms of CL's neuroprotection are not entirely clear. The present study aimed to investigate the effects and mechanisms of CL-mediated neuroprotection through Caenorhabditis elegans models...

Communication between mesodermal cells and epithelial cells is fundamental to normal animal development and is frequently disrupted in cancer. However, the genes and processes that mediate this communication are incompletely understood. To identify genes that mediate this communication and alter the proliferation of cells with an oncogenic Ras genotype, we carried out a tissue-specific genome-wide RNAi screen in C. elegans animals bearing a let-60(n1046gf) (RasG13E) allele. The screen identifies 24 genes that, when knocked down in adjacent mesodermal tissue, suppress the increased vulval epithelial cell proliferation defect associated with let-60(n1046gf)...

Synaptic connections are essential to build a functional brain. How synapses are formed during development is a fundamental question in neuroscience. Recent studies provided evidence that the gut plays an important role in neuronal development through processing signals derived from gut microbes or nutrients. Defects in gut-brain communication can lead to various neurological disorders. Although the roles of the gut in communicating signals from its internal environment to the brain are well known, it remains unclear whether the gut plays a genetically encoded role in neuronal development...

Coordination of inter-tissue stress signaling is essential for organismal fitness. Neuronal mitochondrial perturbations activate the mitochondrial unfolded-protein response (UPRmt ) in the intestine via the mitokine Wnt signaling in Caenorhabditis elegans. Here, we found that the protein disulfide isomerase PDI-6 coordinates inter-tissue UPRmt signaling via regulating the Wnt ligand EGL-20. PDI-6 is expressed in the endoplasmic reticulum (ER) and interacts with EGL-20 through disulfide bonds that are essential for EGL-20 stability and secretion...

Patterning of the anterior-posterior axis is fundamental to animal development. The Wnt pathway plays a major role in this process by activating the expression of posterior genes in animals from worms to humans. This observation raises the question of whether the Wnt pathway or other regulators control the expression of the many anterior-expressed genes. We found that the expression of five anterior-specific genes in Caenorhabditis elegans embryos depends on the Wnt pathway effectors pop-1/TCF and sys-1/β-catenin...

Cell polarity is regulated by both intrinsic properties of the cell and extrinsic factors in the environment. Wnts are secreted glycoproteins in graded distribution, and they function as morphogens to instruct cell fate and as guidance cues to steer axon growth cone, respectively. Recent studies suggest that Wnts also instruct cell polarization in diverse contexts, by engaging cytoskeletal machineries or transcriptional mechanisms. Here we review the literature of cell polarity control by Wnt glycoproteins, with an emphasis on the nematode Caenorhabditis elegans, a multi-cellular organism in which the importance of polarity-inducing factors can be verified in vivo...

Transcription factors are key players in gene networks controlling cell fate specification during development. In multicellular organisms, they display complex patterns of expression and binding to their targets, hence, tissue specificity is required in the characterization of transcription factor-target interactions. We introduce here targeted DamID (TaDa) as a method for tissue-specific transcription factor target identification in intact Caenorhabditis elegans animals. We use TaDa to recover targets in the epidermis for two factors, the HES1 homolog LIN-22, and the NR5A1/2 nuclear hormone receptor NHR-25...

The Axin family of scaffolding proteins regulates a wide array of developmental and post-developmental processes in eukaryotes. Studies in the nematode Caenorhabditis elegans have shown that the Axin homolog PRY-1 plays essential roles in multiple tissues. To understand the genetic network of pry-1, we focused on a set of genes that are differentially expressed in the pry-1-mutant transcriptome and are linked to reproductive structure development. Knocking down eight of the genes (spp-1, clsp-1, ard-1, rpn-7, cpz-1, his-7, cdk-1, and rnr-1) via RNA interference efficiently suppressed the multivulva phenotype of pry-1 mutants...

Neurons form elaborate networks by guiding axons and dendrites to appropriate destinations. Neurites require information about the relative body axes during the initial projection from the cell body, and failure to receive or interpret those cues correctly can result in outgrowth errors. We identified a mutation in the Ig superfamily member syg-2 in a screen for animals with anterior/posterior (A/P) axon guidance defects. We found that syg-2 and its cognate Ig family member syg-1 appear to function in a linear genetic pathway to control the outgrowth of GABAergic axons...

Migration of neuroblasts and neurons from their birthplace is central to the formation of neural circuits and networks. ETR-1 is the Caenorhabditis elegans homolog of the CELF1 (CUGBP, ELAV-like family 1) RNA-processing factor involved in neuromuscular disorders. etr-1 regulates body wall muscle differentiation. Our previous work showed that etr-1 in muscle has a non-autonomous role in neuronal migration, suggesting that ETR-1 is involved in the production of a signal emanating from body wall muscle that controls neuroblast migration and that interacts with Wnt signaling...

Gelsemium elegans ( G. elegans ) Benth., recognized as a toxic plant, has been used as traditional Chinese medicine for the treatment of neuropathic pain and cancer for many years. In the present study, we aim to obtain the anti-tumor effects of alkaloids of G. elegans and their active components in hepatocellular carcinoma (HCC) and the potential mechanism was also further investigated. We demonstrated that sempervirine induced HCC cells apoptosis and the apoptosis was associated with cell cycle arrest during the G1 phase, up-regulation of p53 and down-regulation of cyclin D1, cyclin B1 and CDK2...

The Wnt family contains conserved secretory proteins required for developmental patterning and tissue homeostasis. However, how Wnt is targeted to the endoplasmic reticulum (ER) for processing and secretion remains poorly understood. Here, we report that CATP-8/P5A ATPase directs neuronal migration non-cell autonomously in Caenorhabditis elegans by regulating EGL-20/Wnt biogenesis. CATP-8 likely functions as a translocase to translocate nascent EGL-20/Wnt polypeptide into the ER by interacting with the highly hydrophobic core region of EGL-20 signal sequence...