Chen L et al. (2015) Curr Genomics "Circular RNAs in Eukaryotic Cells."

Shan G, Huang C, Chen L, Wang X

[Curr Genomics, 2015]

Circular RNAs (circRNAs) are now recognized as large species of transcripts in eukaryotic cells. From model organisms such as C. elegans, Drosophila, mice to human beings, thousands of circRNAs formed from back-splicing of exons have been identified. The known complexity of transcriptome has been greatly expanded upon the discovery of these RNAs. Studies about the biogenesis and physiological functions have yielded substantial knowledge for the circRNAs, and they are now more likely to be viewed as regulatory elements coded by the genome rather than unavoidable noise of gene expression. Certain human diseases may also relate to circRNAs. These circRNAs show diversifications in features such as sequence composition and cellular localization, and thus we propose that they may be divided into subtypes such as cytoplasmic circRNAs, nuclear circRNAs, and exon-intron circRNAs (EIciRNAs). Here we summarize and discuss knowns and unknowns for these RNAs, and we need to keep in mind that the whole field is still at the beginning of exciting explorations.

Chen L (2018) Mol Cell Neurosci "Microtubules and axon regeneration in C. elegans."

Chen L

[Mol Cell Neurosci, 2018]

Axon regeneration is a fundamental and conserved process that allows the nervous system to repair circuits after trauma. Due to its conserved genome, transparent body, and relatively simple neuroanatomy, C. elegans has become a powerful model organism for studying the cellular and molecular mechanisms underlying axon regeneration. Various studies from different model organisms have found microtubule dynamics to be pivotal to axon regrowth. In this review, we will discuss the latest findings on how microtubule dynamics are regulated during axon regeneration in C. elegans. Understanding the mechanisms of axon regeneration will aid in the development of more effective therapeutic strategies for treatments of diseases involving disconnection of axons, such as spinal cord injury and stroke.

Chen L et al. (2010) Dev Dyn ""CRASH"ing with the worm: insights into L1CAM functions and mechanisms."

Zhou S, Chen L

[Dev Dyn, 2010]

The L1 family of cell adhesion molecules (L1CAMs) in vertebrates has long been studied for its roles in nervous system development and function. Members of this family have been associated with distinct neurological disorders that include CRASH, autism, 3p syndrome, and schizophrenia. The conservation of L1CAMs in Drosophila and Caenorhabditis elegans allows the opportunity to take advantage of these simple model organisms and their accessible genetic manipulations to dissect L1CAM functions and mechanisms of action. This review summarizes the discoveries of L1CAMs made in C. elegans, showcasing this simple model organism as a powerful system to uncover L1CAM mechanisms and roles in healthy and diseased states.

Chen L et al. (2020) J Nanosci Nanotechnol "Toxicological Evaluation of Graphene-Family Nanomaterials."

Gu Z, Yan L, Zhang A, Li J, Chen Z, Chen L, Zhao F

[J Nanosci Nanotechnol, 2020]

With the extending applications, graphene-family nanomaterials begin to enter people's life via various ways, largely increasing the exposure frequencies. In spite of the increasing toxicological studies, the biosafety of graphene-based nanomaterials still remains elusive. Graphene oxide (GO), an oxidation derivative of graphene, is considered as one of the recently-emerging nanomaterials attractive for biomedical applications. Accompanied with the prospect of applications are the great concerns about its biosafety for human and environment. Herein, this review intends to systematically summarize the research on GO toxicity both <i>in vitro</i> and <i>in vivo</i> followed by deep discussions about the toxicological mechanisms. The currently reported toxicity of GO mainly includes inhalation toxicity, ingestion toxicity, dermal toxicity and hemocompatibility depending on exposure routes. The toxicity evaluation of GO using non-rodent organisms (zebrafish, <i>Caenorhabditis elegans</i> and drosophila, etc.) is also summarized, supplementary to <i>in vivo</i> toxicity of GO. Based on the comprehensive summary of the reported GO-induced toxicity, our review suggests considerable emphasis being put on the balance of benefits and risks when employing the nanotechnology.

Chen L et al. (2022) Cell Rep "Escape steering by cholecystokinin peptidergic signaling."

Chen L, Liu Y, Zhang Y, Ge MH, Hung W, Chen LM, Su P, Gao S, Tao L, Zhen M, Li H, Wang Y, Wu ZX, Mao H, Yue Z, Fei P

[Cell Rep, 2022]

Escape is an evolutionarily conserved and essential avoidance response. Considered to be innate, most studies on escape responses focused on hard-wired circuits. We report here that a neuropeptide NLP-18 and its cholecystokinin receptor CKR-1 enable the escape circuit to execute a full omega (&#937;) turn. We demonstrate in vivo NLP-18 is mainly secreted by the gustatory sensory neuron (ASI) to activate CKR-1 in the head motor neuron (SMD) and the turn-initiating interneuron (AIB). Removal of NLP-18 or CKR-1 or specific knockdown of CKR-1 in SMD or AIB neurons leads to shallower turns, hence less robust escape steering. Consistently, elevation of head motor neuron (SMD)'s Ca2+ transients during escape steering is attenuated upon the removal of NLP-18 or CKR-1. In vitro, synthetic NLP-18 directly evokes CKR-1-dependent currents in oocytes and CKR-1-dependent Ca2+ transients in SMD. Thus, cholecystokinin peptidergic signaling modulates an escape circuit to generate robust escape steering.

Chen L et al. (2011) Trends Cell Biol "Axon regeneration mechanisms: insights from C. elegans."

Chisholm AD, Chen L

[Trends Cell Biol, 2011]

Understanding the mechanisms of axon regeneration is of great importance to the development of therapeutic treatments for spinal cord injury or stroke. Axon regeneration has long been studied in diverse vertebrate and invertebrate models, but until recently had not been analyzed in the genetically tractable model organism Caenorhabditis elegans. The small size, simple neuroanatomy, and transparency of C. elegans allows single fluorescently labeled axons to be severed in live animals using laser microsurgery. Many neurons in C. elegans are capable of regenerative regrowth, and can in some cases re-establish functional connections. Large-scale genetic screens have begun to elucidate the genetic basis of axon regrowth.

Chen L et al. (2018) Genetics "Establishment of Signaling Interactions with Cellular Resolution for Every Cell Cycle of Embryogenesis."

Ho VWS, Ng HCK, Zhao Z, Ren X, Yan H, Chan LY, Huang X, Wong MK, Chen L

[Genetics, 2018]

Intercellular signaling interaction plays a key role in breaking fate symmetry during animal development. Identification of the signaling interaction at cellular resolution is technically challenging, especially in a developing embryo. Here we develop a platform that allows automated inference and validation of signaling interaction for every cell cycle of<i>C. elegans</i>embryogenesis. This is achieved by generation of a systems-level cell contact map that consists of 1,114 highly confident intercellular contacts by modeling analysis and is validated through cell membrane labeling coupled with cell lineage analysis. We apply the map to identify cell pairs between which a Notch signaling interaction takes place. By generating expression patterns for two ligands and two receptors of Notch signaling pathway with cellular resolution using automated expression profiling technique, we are able to refine existing and identify novel Notch interactions during<i>C. elegans</i>embryogenesis. Targeted cell ablation followed by cell lineage analysis demonstrates the roles of signaling interactions over cell division in breaking fate symmetry. We finally develop a website that allows online access to the cell-cell contact map for mapping of other signaling interaction in the community. The platform can be adapted to establish cellular interaction from any other signaling pathways.

Chen L et al. (2016) Worm "A joint graph inference case study: the C. elegans chemical and electrical connectomes."

Vogelstein JT, Priebe CE, Chen L, Lyzinski V

[Worm, 2016]

We investigate joint graph inference for the chemical and electrical connectomes of the Caenorhabditis elegans roundworm. The C. elegans connectomes consist of [Formula: see text] non-isolated neurons with known functional attributes, and there are two types of synaptic connectomes, resulting in a pair of graphs. We formulate our joint graph inference from the perspectives of seeded graph matching and joint vertex classification. Our results suggest that connectomic inference should proceed in the joint space of the two connectomes, which has significant neuroscientific implications.

Chen L et al. (2024) Cells "Amyotrophic Lateral Sclerosis Mechanism: Insights from the Caenorhabditis elegans Models."

Gao S, Zhang S, Liu S, Chen L

[Cells, 2024]

Amyotrophic Lateral Sclerosis (ALS) is a debilitating neurodegenerative condition characterized by the progressive degeneration of motor neurons. Despite extensive research in various model animals, the cellular signal mechanisms of ALS remain elusive, impeding the development of efficacious treatments. Among these models, a well-characterized and diminutive organism, <i>Caenorhabditis elegans</i> (<i>C. elegans</i>), has emerged as a potent tool for investigating the molecular and cellular dimensions of ALS pathogenesis. This review summarizes the contributions of <i>C. elegans</i> models to our comprehension of ALS, emphasizing pivotal findings pertaining to genetics, protein aggregation, cellular pathways, and potential therapeutic strategies. We analyze both the merits and constraints of the <i>C. elegans</i> system in the realm of ALS research and point towards future investigations that could bridge the chasm between <i>C. elegans</i> foundational discoveries and clinical applications.

Chen L et al. (2016) PLoS One "rBmTX14 Increases the Life Span and Promotes the Locomotion of Caenorhabditis Elegans."

Huang Z, Chen L, Xu J, Li W, Liu X, Liu Y, Wan L, Zhang J, Xiang J, Zhang R, Teng K

[PLoS One, 2016]

The scorpion has been extensively used in various pharmacological profiles or as food supplies. The exploration of scorpion venom has been reported due to the presence of recombinant peptides. rBmTX14 is an alpha-neurotoxin extracted from the venom gland of the East Asian scorpion Buthus martensii Karsch and can affect ion channel conductance. Here, we investigated the functions of rBmTX14 using the Caenorhabditis elegans model. Using western blot analysis, rBmTX14 was shown to be expressed both in the cytoplasm and inclusion bodies in the E.coli Rosetta (DE3) strain. Circular dichroism spectroscopy analysis demonstrated that purified rBmTX14 retained its biological structures. Next, feeding nematodes with E.coli Rosetta (DE3) expressing rBmTX14 caused extension of the life span and promoted the locomotion of the nematodes. In addition, we identified several genes that play various roles in the life span and locomotion of C. elegans through microarray analysis and quantitative real-time PCR. Furthermore, if the amino acid site H15 of rBmTX14 was mutated, rBmTX14 no longer promoted the C. elegans life span. In conclusion, the results not only demonstrated the functions and mechanism of rBmTX14 in C. elegans, but also provided the new sight in the utility of recombinant peptides from scorpion venom.