Wang C et al. (2009) Annu Rev Genet "The role of mitochondria in apoptosis*."

Youle RJ, Wang C

[Annu Rev Genet, 2009]

Mitochondria play key roles in activating apoptosis in mammalian cells. Bcl-2 family members regulate the release of proteins from the space between the mitochondrial inner and outer membrane that, once in the cytosol, activate caspase proteases that dismantle cells and signal efficient phagocytosis of cell corpses. Here we review the extensive literature on proteins released from the intermembrane space and consider genetic evidence for and against their roles in apoptosis activation. We also compare and contrast apoptosis pathways in Caenorhabditis elegans, Drosophila melanogaster, and mammals that indicate major mysteries remaining to be solved.

Wang C et al. (2021) Cytometry A "Innovative fluorescent probes for in vivo visualization of biomolecules in living Caenorhabditis elegans."

Zhu Y, Zhang H, Wang C, Xia C

[Cytometry A, 2021]

Caenorhabditis elegans (C. elegans) as a well-established multicellular model organism has been widely used in the biological field for half a century. Its numerous advantages including small body size, rapid life cycle, high-reproductive rate, well-defined anatomy, and conserved genome, has made C. elegans one of the most successful multicellular model organisms. Discoveries obtained from the C. elegans model have made great contributions to research fields such as development, aging, biophysics, immunology, and neuroscience. Because of its transparent body and giant cell size, C. elegans is also an ideal subject for high resolution and high-throughput optical imaging and analysis. During the past decade, great advances have been made to develop biomolecule-targeting techniques for noninvasive optical imaging. These novel technologies expanded the toolbox for qualitative and quantitative analysis of biomolecules in C. elegans. In this review, we summarize recently developed fluorescent probes or labeling techniques for visualizing biomolecules at the cellular, subcellular or molecular scale by using C. elegans as the major model organism or designed specifically for the applications in C. elegans. Combining the technological advantages of the C. elegans model with the novel fluorescent labeling techniques will provide new horizons for high-efficiency quantitative optical analysis in live organisms.

Wang C et al. (2022) Front Pharmacol "Using Caenorhabditis elegans to Model Therapeutic Interventions of Neurodegenerative Diseases Targeting Microbe-Host Interactions."

Zheng C, Wang C

[Front Pharmacol, 2022]

Emerging evidence from both clinical studies and animal models indicates the importance of the interaction between the gut microbiome and the brain in the pathogenesis of neurodegenerative diseases (NDs). Although how microbes modulate neurodegeneration is still mostly unclear, recent studies have started to probe into the mechanisms for the communication between microbes and hosts in NDs. In this review, we highlight the advantages of using Caenorhabditis elegans (C. elegans) to disentangle the microbe-host interaction that regulates neurodegeneration. We summarize the microbial pro- and anti-neurodegenerative factors identified using the C. elegans ND models and the effects of many are confirmed in mouse models. Specifically, we focused on the role of bacterial amyloid proteins, such as curli, in promoting proteotoxicity and neurodegeneration by cross-seeding the aggregation of endogenous ND-related proteins, such as α-synuclein. Targeting bacterial amyloid production may serve as a novel therapeutic strategy for treating NDs, and several compounds, such as epigallocatechin-3-gallate (EGCG), were shown to suppress neurodegeneration at least partly by inhibiting curli production. Because bacterial amyloid fibrils contribute to biofilm formation, inhibition of amyloid production often leads to the disruption of biofilms. Interestingly, from a list of 59 compounds that showed neuroprotective effects in C. elegans and mouse ND models, we found that about half of them are known to inhibit bacterial growth or biofilm formation, suggesting a strong correlation between the neuroprotective and antibiofilm activities. Whether these potential therapeutics indeed protect neurons from proteotoxicity by inhibiting the cross-seeding between bacterial and human amyloid proteins awaits further investigations. Finally, we propose to screen the long list of antibiofilm agents, both FDA-approved drugs and novel compounds, for their neuroprotective effects and develop new pharmaceuticals that target the gut microbiome for the treatment of NDs. To this end, the C. elegans ND models can serve as a platform for fast, high-throughput, and low-cost drug screens that target the microbe-host interaction in NDs.

Wang Z et al. (2011) Methods Cell Biol "Dissection of genetic pathways in C. elegans."

Sherwood DR, Wang Z

[Methods Cell Biol, 2011]

With unique genetic and cell biological strengths, C. elegans has emerged as a powerful model system for studying many biological processes. These processes are typically regulated by complex genetic networks consisting of genes. Identifying those genes and organizing them into genetic pathways are two major steps toward understanding the mechanisms that regulate biological events. Forward genetic screens with various designs are a traditional approach for identifying candidate genes. The completion of the genome sequencing in C. elegans and the advent of high-throughput experimental techniques have led to the development of two additional powerful approaches: functional genomics and systems biology. Genes that are discovered by these approaches can be ordered into interacting pathways through a variety of strategies, involving genetics, cell biology, biochemistry, and functional genomics, to gain a more complete understanding of how gene regulatory networks control a particular biological process. The aim of this review is to provide an overview of the approaches available to identify and construct the genetic pathways using C. elegans.

Hu W et al. (2022) J Appl Toxicol "Toxicity of transition metal nanoparticles: a review of different experimental models in the gastrointestinal tract."

Liang Q, Gao D, Wang C, Hu W

[J Appl Toxicol, 2022]

The development of nanotechnology is becoming a major trend nowadays. Nanoparticles (NPs) have been widely used in fields including food, biomedicine, cosmetics, endowing NPs more opportunities to enter the human body. It is well known that the gut microbiome plays a key role in human health, and the exposure of intestines to NPs is unavoidable. Accordingly, the toxicity of NPs has attracted more attention than before. This review mainly highlights recent advances in the evaluation of NPs' toxicity in the gastrointestinal system. From the existing cell-based experimental models, such as the original mono-culture models, co-culture models, 3D-culture models, the models established on microfluidic chips, to those in vivo experiments, such as mice models, Caenorhabditis elegans models, zebrafish models, human volunteers, as well as computer-simulated toxicity models. Owing to these models, especially those more biomimetic models, the outcome of the toxicity of NPs acting in the gastrointestinal tract can get results closer to what happened inside the real human micro-environment.

Chen H et al. (2019) J Environ Manage "A review of toxicity induced by persistent organic pollutants (POPs) and endocrine-disrupting chemicals (EDCs) in the nematode Caenorhabditis elegans."

Chen X, Yu Z, Yu Y, Li H, Hua X, Ma R, Li L, Xiang M, Chen H, Wang C

[J Environ Manage, 2019]

Persistent organic pollutants (POPs) and endocrine disrupting compounds (EDCs) are almost ubiquitous in synthetic and natural sources; however these contaminants adversely impact ecosystems and humans. Owing to their potential toxicity, concerns have been raised about the effects of POPs and EDCs on ecological and human health. Therefore, toxicity evaluation and mechanisms actions of these contaminants are of great interest. The nematode Caenorhabditis elegans (C. elegans), an excellent model animal for environmental toxicology research, has been used widely for toxicity studies of POPs or EDCs from the whole-animal level to the single-cell level. In this review, we have discussed the toxicity of specific POPs or EDCs after acute, chronic, and multigenerational exposure in C. elegans. We have also introduced a discussion of the toxicological mechanisms of these compounds in C. elegans, with respect to oxidative stress, cell apoptosis, and the insulin/IGF-1 signaling pathway. Finally, we raised considered the perspectives and challenges of the toxicity assessments, multigenerational toxicity, and toxicological mechanisms.

Scholey JM et al. (2004) Biochem Soc Trans "Intraflagellar transport motors in Caenorhabditis elegans neurons."

Scholey JM, Ou G, Gunnarson A, Snow J

[Biochem Soc Trans, 2004]

IFT (intraflagellar transport) assembles and maintains sensory cilia on the dendritic endings of chemosensory neurons within the nematode Caenorhabditis elegans. During IFT, macromolecular protein complexes called IFT particles (which carry ciliary precursors) are moved from the base of the sensory cilium to its distal tip by anterograde IFT motors (kinesin-II and Osm-3 kinesin) and back to the base by retrograde IFT-dynein [Rosenbaum and Witman (2002) Nat. Rev. Mol. Cell Biol. 3, 813-825; Scholey (2003) Annu. Rev. Cell Dev. Biol. 19, 423-443; and Snell, Pan and Wang (2004) Cell 117, 693-697]. In the present study, we describe the protein machinery of IFT in C. elegans, which we have analysed using time-lapse fluorescence microscopy of green fluorescent protein-fusion proteins in concert with ciliary mutants.

Wang MQ et al. (2001) Curr Top Dev Biol "Pattern formation during C. elegans vulval induction."

Wang MQ, Sternberg PW

[Curr Top Dev Biol, 2001]

Studies of C. elegans vulval development provide insights into the process of pattern formation during animal development. The invariant pattern of vulval precursor cell fates is specified by the integration of at least two signaling systems. Recent findings suggest that multiple, partially redundant mechanisms are involved in patterning the vulval precursor cells. The inductive signal activates the LET-60/RAS signaling pathway and induces the 1 degree fate, whereas the lateral signal mediated by LIN-12/Notch is required for specification of the 2 degrees fate. Several regulatory pathways antagonize the RAS signaling pathway and specify the non-vulval 3 degrees fate in the absence of induction. The temporal and spatial regulation of VPC competence and production of the inductive and the lateral signal are precisely coordinated to ensure the wild-type vulval pattern.

Wang X et al. (2020) Front Cell Dev Biol "Diverse Roles of PUF Proteins in Germline Stem and Progenitor Cell Development in C. elegans."

Voronina E, Wang X

[Front Cell Dev Biol, 2020]

Stem cell development depends on post-transcriptional regulation mediated by RNA-binding proteins (RBPs) (Zhang et al., 1997; Forbes and Lehmann, 1998; Okano et al., 2005; Ratti et al., 2006; Kwon et al., 2013). Pumilio and FBF (PUF) family RBPs are highly conserved post-transcriptional regulators that are critical for stem cell maintenance (Wickens et al., 2002; Quenault et al., 2011). The RNA-binding domains of PUF proteins recognize a family of related sequence motifs in the target mRNAs, yet individual PUF proteins have clearly distinct biological functions (Lu et al., 2009; Wang et al., 2018). The <i>C. elegans</i> germline is a simple and powerful model system for analyzing regulation of stem cell development. Studies in <i>C. elegans</i> uncovered specific physiological roles for PUFs expressed in the germline stem cells ranging from control of proliferation and differentiation to regulation of the sperm/oocyte decision. Importantly, recent studies started to illuminate the mechanisms behind PUF functional divergence. This review summarizes the many roles of PUF-8, FBF-1, and FBF-2 in germline stem and progenitor cells (SPCs) and discusses the factors accounting for their distinct biological functions. PUF proteins are conserved in evolution, and insights into PUF-mediated regulation provided by the <i>C. elegans</i> model system are likely relevant for other organisms.

Li H et al. (2022) Environ Pollut "Review of the toxicity and potential molecular mechanisms of parental or successive exposure to environmental pollutants in the model organism Caenorhabditis elegans."

Li Y, Wang C, Cheng B, Zeng L, Huang Y, Chen C, Shi C, Zhang J, Chen H, Li H, Peng Y, Xiang M

[Environ Pollut, 2022]

Environmental pollutants such as heavy metals, nano/microparticles, and organic compounds have been detected in a wide range of environmental media, causing long-term exposure in various organisms and even humans through breathing, contacting, ingestion, and other routes. Long-term exposure to environmental pollutants in organisms or humans promotes exposure of offspring to parental and environmental pollutants, and subsequently results in multiple biological defects in the offspring. This review dialectically summarizes and discusses the existing studies using Caenorhabditis elegans (C. elegans) as a model organism to explore the multi/transgenerational toxicity and potential underlying molecular mechanisms induced by environmental pollutants following parental or successive exposure patterns. Parental and successive exposure to environmental pollutants induces various biological defects in C. elegans across multiple generations, including multi/transgenerational developmental toxicity, neurotoxicity, reproductive toxicity, and metabolic disturbances, which may be transmitted to progeny through reactive oxygen species-induced damage, epigenetic mechanisms, insulin/insulin-like growth factor-1 signaling pathway. This review aims to arouse researchers' interest in the multi/transgenerational toxicity of pollutants and hopes to explore the possible long-term effects of environmental pollutants on organisms and even humans, as well as to provide constructive suggestions for the safety and management of emerging alternatives.