Yu R et al. (2016) Cell "CSR-1 Slices a Balance."

Moazed D, Yu R

[Cell, 2016]

CSR-1 is a germline-expressed C. elegans Argonaute protein essential for viability. In this issue of Cell, Gerson-Gurwitz et al. now demonstrate a role for CSR-1 and its slicer activity in downregulating the levels of maternally deposited mRNAs to fine-tune the expression of proteins with critical roles in embryonic cell divisions.

Yu, A. et al. (2017) International Worm Meeting "Non-associative learning as a behavioral strategy to promote dispersal."

Rankin, C., Yu, A., Ardiel, E.

[International Worm Meeting, 2017]

Habituation is a form of non-associative learning defined as decremented likelihood and/or magnitude in response to repeatedly presented stimuli. Habituation is thought to help animal ignore recurring innocuous events and free up its neural resources to attend to other novel or salient stimuli in the environment. C. elegans is known to habituate to harmless stimuli such as non-localized tap (Rankin et al., 1990). Recently, we have reported that worms also displayed behavioral characteristics of habituation when a pair of nociceptor neurons, ASH, were repeatedly stimulated with optogenetics (Ardiel et al., 2016). Because ASH detects natural aversive stimuli that are harmful and potentially lethal to worms, it seems puzzling that animals habituate to these noxious stimuli. Our analysis used a non-response-centric approach and found that habituation of ASH-mediated reversal responses are accompanied by the simultaneous sensitization of forward locomotion (Ardiel et al., 2017, unpublished). This behavioral plasticity was found to be mediated by the Pigment Dispersal Factor (PDF) signaling pathway. These coordinated changes in different behavioral components form an optimal behavioral strategy to guide animals to spend less time responding to the recurrent noxious stimuli and more time moving away from them. In this present study, we investigated whether tap habituation was associated with changes in other behavioral components. We observed similar patterns of behavioral plasticity in tap habituation that is also mediate by PDF signaling. Our findings suggest that different forms of non-associative learning participate in a suite of coordinated behavioral changes that together promote a shift in behavioral strategy. Our study also highlights the needs for more detailed behavioral analyses.

Yu G et al. (2019) Int J Mol Sci "The Epigenetics of Aging in Invertebrates."

Yang M, Gao Y, Wu Q, Chen M, Yu G

[Int J Mol Sci, 2019]

Aging is an unstoppable process coupled to the loss of physiological function and increased susceptibility to diseases. Epigenetic alteration is one of the hallmarks of aging, which involves changes in DNA methylation patterns, post-translational modification of histones, chromatin remodeling and non-coding RNA interference. Invertebrate model organisms, such as <i>Drosophila melanogaster</i> and <i>Caenorhabditis elegans</i>, have been used to investigate the biological mechanisms of aging because they show, evolutionarily, the conservation of many aspects of aging. In this review, we focus on recent advances in the epigenetic changes of aging with invertebrate models, providing insight into the relationship between epigenetic dynamics and aging.

Yu J et al. (2017) eNeuro "An Aversive Response to Osmotic Upshift in Caenorhabditis elegans."

Liu H, Yu J, Yang W, Zhang Y, Hao Y

[eNeuro, 2017]

Environmental osmolarity presents a common type of sensory stimulus to animals. While behavioral responses to osmotic changes are important for maintaining a stable intracellular osmolarity, the underlying mechanisms are not fully understood. In the natural habitat of Caenorhabditis elegans, changes in environmental osmolarity are commonplace. It is known that the nematode acutely avoids shocks of extremely high osmolarity. Here, we show that C. elegans also generates gradually increased aversion of mild upshifts in environmental osmolarity. Different from an acute avoidance of osmotic shocks that depends on the function of a transient receptor potential vanilloid channel, the slow aversion to osmotic upshifts requires the cGMP-gated sensory channel subunit TAX-2. TAX-2 acts in several sensory neurons that are exposed to body fluid to generate the aversive response through a motor network that underlies navigation. Osmotic upshifts activate the body cavity sensory neuron URX, which is known to induce aversion upon activation. Together, our results characterize the molecular and cellular mechanisms underlying a novel sensorimotor response to osmotic stimuli and reveal that C. elegans engages different behaviors and the underlying mechanisms to regulate responses to extracellular osmolarity.

Yu CJ et al. (2020) Elife "Expansion microscopy of C. elegans."

Chen F, Bhattacharya A, Barry NC, Sinha A, Asano S, Hobert O, Goodman MB, Yu CJ, Boyden ES, Zhang C, Wassie AT, Haspel G

[Elife, 2020]

We recently developed expansion microscopy (ExM), which achieves nanoscale-precise imaging of specimens at ~70 nm resolution (with ~4.5x linear expansion) by isotropic swelling of chemically processed, hydrogel-embedded tissue. ExM of <i>C. elegans</i> is challenged by its cuticle, which is stiff and impermeable to antibodies. Here we present a strategy, expansion of <i>C. elegans</i> (ExCel), to expand fixed, intact <i>C. elegans</i>. ExCel enables simultaneous readout of fluorescent proteins, RNA, DNA location, and anatomical structures at resolutions of ~65-75 nm (3.3-3.8x linear expansion). We also developed epitope-preserving ExCel, which enables imaging of endogenous proteins stained by antibodies, and iterative ExCel, which enables imaging of fluorescent proteins after 20x linear expansion. We demonstrate the utility of the ExCel toolbox for mapping synaptic proteins, for identifying previously unreported proteins at cell junctions, and for gene expression analysis in multiple individual neurons of the same animal.

Yu TW et al. (2001) Nature Neuroscience "Dynamic regulation of axon guidance."

Bargmann CI, Yu TW

[Nature Neuroscience, 2001]

To reach their proper targets, axons rely upon the actions of highly conserved families of attractive and repulsive guidance molecules, including the netrins, Slits, semaphorins and ephrins. These guidance systems are used to generate an astonishingly varied set of neuronal circuits. Here we consider the mechanisms by which a few guidance systems can be used to generate diverse outcomes. Recent studies have revealed extensive transcriptional and post-transcriptional regulation of guidance cues and their regulators, as well as combinatorial mechanisms that integrate information from different families of guidance cues.

Yu YV et al. (2022) Brain Sci "Multisensory Integration in Caenorhabditis elegans in Comparison to Mammals."

Chen Y, Xue W, Yu YV

[Brain Sci, 2022]

Multisensory integration refers to sensory inputs from different sensory modalities being processed simultaneously to produce a unitary output. Surrounded by stimuli from multiple modalities, animals utilize multisensory integration to form a coherent and robust representation of the complex environment. Even though multisensory integration is fundamentally essential for animal life, our understanding of the underlying mechanisms, especially at the molecular, synaptic and circuit levels, remains poorly understood. The study of sensory perception in Caenorhabditis elegans has begun to fill this gap. We have gained a considerable amount of insight into the general principles of sensory neurobiology owing to C. elegans' highly sensitive perceptions, relatively simple nervous system, ample genetic tools and completely mapped neural connectome. Many interesting paradigms of multisensory integration have been characterized in C. elegans, for which input convergence occurs at the sensory neuron or the interneuron level. In this narrative review, we describe some representative cases of multisensory integration in C. elegans, summarize the underlying mechanisms and compare them with those in mammalian systems. Despite the differences, we believe C. elegans is able to provide unique insights into how processing and integrating multisensory inputs can generate flexible and adaptive behaviors. With the emergence of whole brain imaging, the ability of C. elegans to monitor nearly the entire nervous system may be crucial for understanding the function of the brain as a whole.

Yu, A. et al. (2019) International Worm Meeting "Neuropeptides differentially mediate facilitatory forms of non-associative learning."

Chew, Y. L., Schafer, W., Ardiel, E., Rankin, C., Yu, A.

[International Worm Meeting, 2019]

Sensitization and dishabituation are two forms of facilitatory non-associative learning produced by novel or noxious stimuli, that both increase the likelihood and/or magnitude of a response. Although these two forms of non-associative learning have similar effects on behaviour, previous research suggests that they emerge at different developmental stages and have non-identical electrophysiological profiles. Research into the cellular and molecular mechanisms of sensitization and dishabituation can help to further differentiate the two forms of learning, and provide insight into the relationship between different forms of non-associative learning. Our studies found that neuropeptides differentially mediate sensitization and dishabituation. Using our high-throughput Multi-Worm Tracker in combination with optogenetics, we established paradigms for cross-modal sensitization and dishabituation. We identified a FLP-20/FRPR-3 peptidergic signalling pathway that specifically mediates tap-induced ASH response sensitization but not dishabituation. The PDF neuropeptide system also mediates sensitization and dishabituation of the ASH response, with the possible involvement of a novel receptor. Taken together, our data suggest that a number of neuropeptide systems underlie different forms of non-associative learning. Unravelling the cellular and molecular mechanisms of non-associative learning will further our understanding of behavioural plasticity.

Yu W et al. Dose Response "Study on Caenorhabditis Elegans as a Combined Model of Microdosimetry and Biology."

Gao J, Chen N, Long H, Tu Y, Yu W, Sun L, Wang Y

[Dose Response]

Microdosimetry is a tool for the investigation of microscopic energy deposition of ionizing radiation. This work used <i>Caenorhabditis</i> elegans as a model to estimate the microdosimetric deposition level at the ⁶⁰Co gamma radiation. Monte Carlo software PHITS was employed to establish irradiated nematodes model. The dose deposition of the entire body and gonad irradiated to 100 Gy was calculated. The injury levels of radiation were evaluated by the detection of biological indicators. The result of microdosimetric experiment suggested that the dose of whole body of nematodes was estimated to be 99.9 +/- 57.8 Gy, ranging from 19.6 to 332.2 Gy. The dose of gonad was predicted to be 129.4 +/- 558.8 Gy (9.5-6597 Gy). The result of biological experiment suggested that there were little changes in the length of nematodes after irradiation. However, times of head thrash per minute and the spawning yield in 3 consecutive days decreased 27.1% and 94.7%, respectively. Nematodes in the irradiated group displayed heterogeneity. Through contour analysis, trends of behavior kinematics and reproductive capacity of irradiated nematodes proved to be consistent with the dose distribution levels estimated by microdosimetric model. Finally, <i>C</i>. elegans presented a suitable combined model of microdosimetry and biology for studying radiation.

Yu Y et al. (2011) Biochem J "HID-1 is a novel player in the regulation of neuropeptide sorting."

Xu T, Yu Y, Wang L, Liu L, Xu P, Xia Z, Song E, Zhan Y, Jiu Y

[Biochem J, 2011]

Peptide hormones and neuropeptides are packaged and stored in a specialized intracellular organelle called the dense core vesicle. It remains elusive how peptide cargoes are correctly sorted. In the present study, we show that a highly conserved Golgi-localized protein named HID-1 acts to prevent mis-sorting of peptide cargoes to lysosomes for degradation via a PtdIns3P-dependent trafficking pathway. Epistasis analysis suggests that rab-2 is epistatic to hid-1.