Do all animals sleep? Sleep has been observed in many vertebrates, and there is a growing body of evidence for sleep-like states in arthropods and nematodes 1–5. Here we show that sleep is also ...present in Cnidaria 6–8, an earlier-branching metazoan lineage. Cnidaria and Ctenophora are the first metazoan phyla to evolve tissue-level organization and differentiated cell types, such as neurons and muscle 9–15. In Cnidaria, neurons are organized into a non-centralized radially symmetric nerve net 11, 13, 15–17 that nevertheless shares fundamental properties with the vertebrate nervous system: action potentials, synaptic transmission, neuropeptides, and neurotransmitters 15–20. It was reported that cnidarian soft corals 21 and box jellyfish 22, 23 exhibit periods of quiescence, a pre-requisite for sleep-like states, prompting us to ask whether sleep is present in Cnidaria. Within Cnidaria, the upside-down jellyfish Cassiopea spp. displays a quantifiable pulsing behavior, allowing us to perform long-term behavioral tracking. Monitoring of Cassiopea pulsing activity for consecutive days and nights revealed behavioral quiescence at night that is rapidly reversible, as well as a delayed response to stimulation in the quiescent state. When deprived of nighttime quiescence, Cassiopea exhibited decreased activity and reduced responsiveness to a sensory stimulus during the subsequent day, consistent with homeostatic regulation of the quiescent state. Together, these results indicate that Cassiopea has a sleep-like state, supporting the hypothesis that sleep arose early in the metazoan lineage, prior to the emergence of a centralized nervous system.
•Cassiopea jellyfish exhibit reversible behavioral quiescence during the night•Cassiopea show reduced responsiveness to stimuli during their quiescent state•The nighttime quiescence is regulated by both homeostatic and circadian systems•Pharmacological studies show evidence of molecular conservation of sleep regulation
Understanding the phylogenetic roots of behaviors sheds light on the evolutionary forces that shape them. Sleep has been observed in worms, flies, zebrafish, and mice. Nath et al. discover that jellyfish have a sleep-like state. This shifts the known root of sleep in the phylogenetic tree prior to the emergence of a centralized nervous system.
The recognition of molecular patterns associated with specific pathogens or food sources is fundamental to ecology and plays a major role in the evolution of predator-prey relationships 1. Recent ...studies showed that nematodes produce an evolutionarily highly conserved family of small molecules, the ascarosides, which serve essential functions in regulating nematode development and behavior 2–4. Here, we show that nematophagous fungi, natural predators of soil-dwelling nematodes 5, can detect and respond to ascarosides. Nematophagous fungi use specialized trapping devices to catch and consume nematodes, and previous studies demonstrated that most fungal species do not produce traps constitutively but rather initiate trap formation in response to their prey 6. We found that ascarosides, which are constitutively secreted by many species of soil-dwelling nematodes, represent a conserved molecular pattern used by nematophagous fungi to detect prey and trigger trap formation. Ascaroside-induced morphogenesis is conserved in several closely related species of nematophagous fungi and occurs only under nutrient-deprived conditions. Our results demonstrate that microbial predators eavesdrop on chemical communication among their metazoan prey to regulate morphogenesis, providing a striking example of predator-prey coevolution. We anticipate that these findings will have broader implications for understanding other interkingdom interactions involving nematodes, which are found in almost any ecological niche on Earth.
► Nematode pheromone ascarosides induce trap formation in nematophagous fungi ► Ascaroside-induced fungal morphogenesis is conserved in several species ► Different nematophagous fungal species display distinct ascaroside response ► Ascarosides constitute a nematode-associated molecular pattern recognized by microbes
Abstract
WormBase (https://wormbase.org/) is a mature Model Organism Information Resource supporting researchers using the nematode Caenorhabditis elegans as a model system for studies across a broad ...range of basic biological processes. Toward this mission, WormBase efforts are arranged in three primary facets: curation, user interface and architecture. In this update, we describe progress in each of these three areas. In particular, we discuss the status of literature curation and recently added data, detail new features of the web interface and options for users wishing to conduct data mining workflows, and discuss our efforts to build a robust and scalable architecture by leveraging commercial cloud offerings. We conclude with a description of WormBase's role as a founding member of the nascent Alliance of Genome Resources.
The nematode C. elegans is an important model for the study of social behaviors. Recent investigations have shown that a family of small molecule signals, the ascarosides, controls population density ...sensing and mating behavior. However, despite extensive studies of C. elegans aggregation behaviors, no intraspecific signals promoting attraction or aggregation of wild-type hermaphrodites have been identified. Using comparative metabolomics, we show that the known ascarosides are accompanied by a series of derivatives featuring a tryptophan-derived indole moiety. Behavioral assays demonstrate that these indole ascarosides serve as potent intraspecific attraction and aggregation signals for hermaphrodites, in contrast to ascarosides lacking the indole group, which are repulsive. Hermaphrodite attraction to indole ascarosides depends on the ASK amphid sensory neurons. Downstream of the ASK sensory neuron, the interneuron AIA is required for mediating attraction to indole ascarosides instead of the RMG interneurons, which previous studies have shown to integrate attraction and aggregation signals from ASK and other sensory neurons. The role of the RMG interneuron in mediating aggregation and attraction is thought to depend on the neuropeptide Y-like receptor NPR-1, because solitary and social C. elegans strains are distinguished by different npr-1 variants. We show that indole ascarosides promote attraction and aggregation in both solitary and social C. elegans strains. The identification of indole ascarosides as aggregation signals reveals unexpected complexity of social signaling in C. elegans, which appears to be based on a modular library of ascarosides integrating building blocks derived from lipid β-oxidation and amino-acid metabolism. Variation of modules results in strongly altered signaling content, as addition of a tryptophan-derived indole unit to repellent ascarosides produces strongly attractive indole ascarosides. Our findings show that the library of ascarosides represents a highly developed chemical language integrating different neurophysiological pathways to mediate social communication in C. elegans.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
WormBase (www.wormbase.org) is a central repository for research data on the biology, genetics and genomics of Caenorhabditis elegans and other nematodes. The project has evolved from its original ...remit to collect and integrate all data for a single species, and now extends to numerous nematodes, ranging from evolutionary comparators of C. elegans to parasitic species that threaten plant, animal and human health. Research activity using C. elegans as a model system is as vibrant as ever, and we have created new tools for community curation in response to the ever-increasing volume and complexity of data. To better allow users to navigate their way through these data, we have made a number of improvements to our main website, including new tools for browsing genomic features and ontology annotations. Finally, we have developed a new portal for parasitic worm genomes. WormBase ParaSite (parasite.wormbase.org) contains all publicly available nematode and platyhelminth annotated genome sequences, and is designed specifically to support helminth genomic research.
Null mutants are essential for analyzing gene function. Here, we describe a simple and efficient method to generate
null mutants using CRISPR/Cas9 and short single stranded DNA oligo repair templates ...to insert a universal 43-nucleotide-long knock-in cassette (STOP-IN) into the early exons of target genes. This STOP-IN cassette has stop codons in all three reading frames and leads to frameshifts, which will generate putative null mutations regardless of the reading frame of the insertion position in exons. The STOP-IN cassette also contains an exogenous Cas9 target site that allows further genome editing and provides a unique sequence that simplifies the identification of successful insertion events via PCR. As a proof of concept, we inserted the STOP-IN cassette at a Cas9 target site in
to generate new putative null alleles by injecting preassembled Cas9 ribonucleoprotein and a short synthetic single stranded DNA repair template containing the STOP-IN cassette and two ∼35-nucleotide-long homology arms identical to the sequences flanking the Cas9 cut site. We showed that these new
alleles phenocopied an existing loss-of-function allele of
We further showed that the new
null alleles could be reverted back to the wild-type sequence by targeting the exogenous Cas9 cut site included in the STOP-IN cassette and providing a single stranded wild-type DNA repair oligo. We applied our STOP-IN method to generate new putative null mutants for 20 additional genes, including three pharyngeal muscle-specific genes (
,
, and
), and reported a high insertion rate (46%) based on the animals we screened. We showed that null mutations of
cause recessive lethality with a severe pumping defect and
null mutants have a mild pumping defect, while
is dispensable for pumping. We expect that the knock-in method using the STOP-IN cassette will facilitate the generation of new null mutants to understand gene function in
and other genetic model organisms.
Sleep is characterized by behavioral quiescence, homeostasis, increased arousal threshold, and rapid reversibility. Understanding how these properties are encoded by a neuronal circuit has been ...difficult, and no single molecular or neuronal pathway has been shown to be responsible for the regulation of sleep. Taking advantage of the well-mapped neuronal connections of Caenorhabditis elegans and the sleep-like states in this animal, we demonstrate the changed properties of both sensory neurons and downstream interneurons that mediate sleep and arousal. The ASH sensory neuron displays reduced sensitivity to stimuli in the sleep-like state, and the activity of the corresponding interneurons in ASH’s motor circuit becomes asynchronous. Restoration of interneuron synchrony is sufficient for arousal. The multilevel circuit depression revealed provides an elegant strategy to promote a robust decrease in arousal while allowing for rapid reversibility of the sleep state.
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•Multiple sensory neurons are dampened during sleep•Coordinated interneuron activity is suppressed in sleep and recovered upon waking•Reversibility of sleep is regulated by activity at the command interneuron level•Similar circuit changes occur in three types of sleep
During C. elegans sleep, sensory neurons are less responsive, and interneurons have asynchronous activity, resulting in a slow response to sensory stimuli. The sleep state can be rapidly reversed by restoring interneuron synchrony.
Diapause arrest in animals such as Caenorhabditis elegans is tightly regulated so that animals make appropriate developmental decisions amidst environmental challenges. Fully understanding diapause ...requires mechanistic insight of both entry and exit from the arrested state. Although a steroid hormone pathway regulates the entry decision into C. elegans dauer diapause, its role in the exit decision is less clear. A complication to understanding steroid hormonal regulation of dauer has been the peculiar fact that steroid hormone mutants such as daf-9 form partial dauers under normal growth conditions. Here, we corroborate previous findings that daf-9 mutants remain capable of forming full dauers under unfavorable growth conditions and establish that the daf-9 partial dauer state is likely a partially exited dauer that has initiated but cannot complete the dauer exit process. We show that the steroid hormone pathway is both necessary for and promotes complete dauer exit, and that the spatiotemporal dynamics of steroid hormone regulation during dauer exit resembles that of dauer entry. Overall, dauer entry and dauer exit are distinct developmental decisions that are both controlled by steroid hormone signaling.
Nematodes are among the most successful animals on earth and include important human pathogens, yet little is known about nematode pheromone systems. A group of small molecules called ascarosides has ...been found to mediate mate finding, aggregation, and developmental diapause in Caenorhabditis elegans, but it is unknown whether ascaroside signaling exists outside of the genus Caenorhabditis.
To determine whether ascarosides are used as signaling molecules by other nematode species, we performed a mass spectrometry-based screen for ascarosides in secretions from a variety of both free-living and parasitic (plant, insect, and animal) nematodes. We found that most of the species analyzed, including nematodes from several different clades, produce species-specific ascaroside mixtures. In some cases, ascaroside biosynthesis patterns appear to correlate with phylogeny, whereas in other cases, biosynthesis seems to correlate with lifestyle and ecological niche. We further show that ascarosides mediate distinct nematode behaviors, such as retention, avoidance, and long-range attraction, and that different nematode species respond to distinct, but overlapping, sets of ascarosides.
Our findings indicate that nematodes utilize a conserved family of signaling molecules despite having evolved to occupy diverse ecologies. Their structural features and level of conservation are evocative of bacterial quorum sensing, where acyl homoserine lactones (AHLs) are both produced and sensed by many species of gram-negative bacteria. The identification of species-specific ascaroside profiles may enable pheromone-based approaches to interfere with reproduction and survival of parasitic nematodes, which are responsible for significant agricultural losses and many human diseases worldwide.
► Diverse nematodes produce species-specific mixtures of ascarosides ► Different nematode species respond to distinct but overlapping sets of ascarosides ► Genetically distinct C. elegans strains produce partially divergent ascaroside blends ► Ascaroside signaling is analogous to bacterial quorum sensing
Heterorhabditis bacteriophora are entomopathogenic nematodes that have evolved a mutualism with Photorhabdus luminescens bacteria to function as highly virulent insect pathogens. The nematode ...provides a safe harbor for intestinal symbionts in soil and delivers the symbiotic bacteria into the insect blood. The symbiont provides virulence and toxins, metabolites essential for nematode reproduction, and antibiotic preservation of the insect cadaver. Approximately half of the 21,250 putative protein coding genes identified in the 77 Mbp high quality draft H. bacteriophora genome sequence were novel proteins of unknown function lacking homologs in Caenorhabditis elegans or any other sequenced organisms. Similarly, 317 of the 603 predicted secreted proteins are novel with unknown function in addition to 19 putative peptidases, 9 peptidase inhibitors and 7 C-type lectins that may function in interactions with insect hosts or bacterial symbionts. The 134 proteins contained mariner transposase domains, of which there are none in C. elegans, suggesting an invasion and expansion of mariner transposons in H. bacteriophora. Fewer Kyoto Encyclopedia of Genes and Genomes Orthologies in almost all metabolic categories were detected in the genome compared with 9 other sequenced nematode genomes, which may reflect dependence on the symbiont or insect host for these functions. The H. bacteriophora genome sequence will greatly facilitate genetics, genomics and evolutionary studies to gain fundamental knowledge of nematode parasitism and mutualism. It also elevates the utility of H. bacteriophora as a bridge species between vertebrate parasitic nematodes and the C. elegans model.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK