Faculty Opinions recommendation of C. elegans screen identifies autophagy genes specific to multicellular organisms.

AbstractMulticellular organisms coordinate tissue specific responses to environmental information via both cell-autonomous and non-autonomous mechanisms. In addition to secreted ligands, recent reports implicated release of small RNAs in regulating gene expression across tissue boundaries. Here, we show that the conserved poly-U specific endoribonuclease ENDU-2 in C. elegans is secreted from the soma and taken-up by the germline to ensure germline immortality at elevated temperature. ENDU-2 binds to mature mRNAs and negatively regulates mRNA abundance both in the soma and the germline. While ENDU-2 promotes RNA decay in the soma directly via its endoribonuclease activity, ENDU-2 prevents misexpression of soma-specific genes in the germline and preserves germline immortality independent of its RNA-cleavage activity. In summary, our results suggest that the secreted RNase ENDU-2 regulates gene expression across tissue boundaries in response to temperature alterations and contributes to maintenance of stem cell immortality, probably via retaining a stem cell specific program of gene expression.

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Context-specific regulation of lysosomal lipolysis through network-level diverting of transcription factor interactions

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2104832118 ◽

2021 ◽

Vol 118 (41) ◽

pp. e2104832118

Author(s):

Vinod K. Mony ◽

Anna Drangowska-Way ◽

Reka Albert ◽

Emma Harrison ◽

Abbas Ghaddar ◽

...

Keyword(s):

Oxidative Stress ◽

Target Gene ◽

Specific Nature ◽

C Elegans ◽

Functional Interactions ◽

Genetic Epistasis ◽

Specific Regulation ◽

Context Specific ◽

Factor Interactions ◽

Multicellular Organisms

Plasticity in multicellular organisms involves signaling pathways converting contexts—either natural environmental challenges or laboratory perturbations—into context-specific changes in gene expression. Congruently, the interactions between the signaling molecules and transcription factors (TF) regulating these responses are also context specific. However, when a target gene responds across contexts, the upstream TF identified in one context is often inferred to regulate it across contexts. Reconciling these stable TF–target gene pair inferences with the context-specific nature of homeostatic responses is therefore needed. The induction of the Caenorhabditis elegans genes lipl-3 and lipl-4 is observed in many genetic contexts and is essential to survival during fasting. We find DAF-16/FOXO mediating lipl-4 induction in all contexts tested; hence, lipl-4 regulation seems context independent and compatible with across-context inferences. In contrast, DAF-16–mediated regulation of lipl-3 is context specific. DAF-16 reduces the induction of lipl-3 during fasting, yet it promotes it during oxidative stress. Through discrete dynamic modeling and genetic epistasis, we define that DAF-16 represses HLH-30/TFEB—the main TF activating lipl-3 during fasting. Contrastingly, DAF-16 activates the stress-responsive TF HSF-1 during oxidative stress, which promotes C. elegans survival through induction of lipl-3. Furthermore, the TF MXL-3 contributes to the dominance of HSF-1 at the expense of HLH-30 during oxidative stress but not during fasting. This study shows how context-specific diverting of functional interactions within a molecular network allows cells to specifically respond to a large number of contexts with a limited number of molecular players, a mode of transcriptional regulation we name “contextualized transcription.”

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Microtubule-dependent ribosome localization in C. elegans neurons

eLife ◽

10.7554/elife.26376 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 16

Author(s):

Kentaro Noma ◽

Alexandr Goncharov ◽

Mark H Ellisman ◽

Yishi Jin

Keyword(s):

Cell Biology ◽

Neuronal Development ◽

Ultrastructural Level ◽

Synthesis Methods ◽

Tissue Specific ◽

C Elegans ◽

Multicellular Organisms ◽

Axonal Trafficking ◽

Insight Into

Subcellular localization of ribosomes defines the location and capacity for protein synthesis. Methods for in vivo visualizing ribosomes in multicellular organisms are desirable in mechanistic investigations of the cell biology of ribosome dynamics. Here, we developed an approach using split GFP for tissue-specific visualization of ribosomes in Caenorhabditis elegans. Labeled ribosomes are detected as fluorescent puncta in the axons and synaptic terminals of specific neuron types, correlating with ribosome distribution at the ultrastructural level. We found that axonal ribosomes change localization during neuronal development and after axonal injury. By examining mutants affecting axonal trafficking and performing a forward genetic screen, we showed that the microtubule cytoskeleton and the JIP3 protein UNC-16 exert distinct effects on localization of axonal and somatic ribosomes. Our data demonstrate the utility of tissue-specific visualization of ribosomes in vivo, and provide insight into the mechanisms of active regulation of ribosome localization in neurons.

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A Dynamic Body Model of the NematodeC. eleganswith Neural Oscillators

Journal of Robotics and Mechatronics ◽

10.20965/jrm.2005.p0318 ◽

2005 ◽

Vol 17 (3) ◽

pp. 318-326 ◽

Cited By ~ 10

Author(s):

Michiyo Suzuki ◽

◽

Takeshi Goto ◽

Toshio Tsuji ◽

Hisao Ohtake ◽

...

Keyword(s):

Computer Simulation ◽

Motor Control ◽

Caenorhabditis Elegans ◽

Neural Circuit ◽

Rhythmic Movement ◽

Circuit Model ◽

Neural Oscillators ◽

C Elegans ◽

Body Model ◽

Multicellular Organisms

The nematode Caenorhabditis elegans (C. elegans), a relatively simple organism in structure, is one of the most well-studied multicellular organisms. We developed a virtual C. elegans based on the actual organism to analyze motor control. We propose a dynamic body model, including muscles, controlled by a neural circuit model based on the actual nematode. The model uses neural oscillators to generate rhythmic movement. Computer simulation confirmed that the virtual C. elegans realizes motor control similar qualitatively to that of the actual organism. Specified classes of neurons are killed in the neural circuit model corresponding to actual unc mutants, demonstrating that resulting movement of the virtual C. elegans resembles that of actual mutants.

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Regulation of the mitosis/meiosis decision in the Caenorhabditis elegans germline

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2003.1333 ◽

2003 ◽

Vol 358 (1436) ◽

pp. 1359-1362 ◽

Cited By ~ 60

Author(s):

Sarah L. Crittenden ◽

Christian R. Eckmann ◽

Liaoteng Wang ◽

David S. Bernstein ◽

Marvin Wickens ◽

...

Keyword(s):

Stem Cells ◽

Caenorhabditis Elegans ◽

Rna Binding ◽

Rna Binding Proteins ◽

Germline Stem Cells ◽

Puf Proteins ◽

C Elegans ◽

Transcriptional Regulatory ◽

Mitotic Proliferation ◽

Multicellular Organisms

During the development of multicellular organisms, the processes of growth and differentiation are kept in balance to generate and maintain tissues and organs of the correct size, shape and cellular composition. We have investigated the molecular controls of growth and differentiation in the Caenorhabditis elegans germline. A single somatic cell, called the distal tip cell, promotes mitotic proliferation in the adjacent germline by GLP–1/Notch signalling. Within the germline, the decisions between mitosis and meiosis and between spermatogenesis and oogenesis are controlled by a group of conserved RNA regulators. FBF, a member of the PUF (for Pumilio and FBF) family of RNA–binding proteins, promotes mitosis by repressing gld–1 mRNA activity; the GLD–1, GLD–2, GLD–3 and NOS–3 proteins promote entry into meiosis by regulating mRNAs that remain unknown. The regulatory balance between opposing FBF and GLD activities is crucial for controlling the extent of germline proliferation. PUF proteins regulate germline stem cells in both Drosophila and C. elegans and are localized to germline stem cells of the mammalian testis. Therefore, this post–transcriptional regulatory switch may be an ancient mechanism for controlling maintenance of stem cells versus differentiation.

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The functional repertoire encoded within the native microbiome of the model nematode Caenorhabditis elegans

10.1101/554345 ◽

2019 ◽

Author(s):

Johannes Zimmermann ◽

Nancy Obeng ◽

Wentao Yang ◽

Barbara Pees ◽

Carola Petersen ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Integrative Approach ◽

Metabolic Modelling ◽

Bacterial Physiology ◽

C Elegans ◽

Pyruvate Fermentation ◽

Bacterial Microbiome ◽

Multicellular Organisms ◽

Taxonomic Characterization

AbstractThe microbiome is generally assumed to have a substantial influence on the biology of multicellular organisms. The exact functional contributions of the microbes are often unclear and cannot be inferred easily from 16S rRNA genotyping, which is commonly used for taxonomic characterization of the bacterial associates. In order to bridge this knowledge gap, we here analyzed the metabolic competences of the native microbiome of the model nematode Caenorhabditis elegans. We integrated whole genome sequences of 77 bacterial microbiome members with metabolic modelling and experimental characterization of bacterial physiology. We found that, as a community, the microbiome can synthesize all essential nutrients for C. elegans. Both metabolic models and experimental analyses further revealed that nutrient context can influence how bacteria interact within the microbiome. We identified key bacterial traits that are likely to influence the microbe’s ability to colonize C. elegans (e.g., pyruvate fermentation to acetoin) and the resulting effects on nematode fitness (e.g., hydroxyproline degradation). Considering that the microbiome is usually neglected in the comprehensive research on this nematode, the resource presented here will help our understanding of C. elegans biology in a more natural context. Our integrative approach moreover provides a novel, general framework to dissect microbiome-mediated functions.

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Microfluidic immobilization and subcellular imaging of developing Caenorhabditis elegans

10.1101/139915 ◽

2017 ◽

Author(s):

Jordan Shivers ◽

Sravanti Uppaluri ◽

Clifford P. Brangwynne

Keyword(s):

Larval Development ◽

Protein Interactions ◽

3D Imaging ◽

Fluorescence Recovery After Photobleaching ◽

Model Organism ◽

Fluorescence Recovery ◽

C Elegans ◽

Nucleolar Proteins ◽

Multicellular Organisms

C. elegans has been an essential model organism in the fields of developmental biology, neuroscience, and aging. However, these areas have been limited by our ability to visualize and track individual C. elegans worms, especially at the subcellular scale, over the course of their lifetime. Here we present a microfluidic device to culture individual C. elegans in parallel throughout post-embryonic development. The device allows for periodic mechanical immobilization of the worm, enabling 3D imaging at subcellular precision. The immobilization is sufficient to enable fluorescence recovery after photobleaching (FRAP) measurements on organelles and other substructures within the same specific cells, throughout larval development, without the use of chemical anesthetics. Using this device, we measure FRAP recovery of two nucleolar proteins in specific intestinal cells within the same worms during larval development. We show that these exhibit different fluorescence recovery as they grow, suggesting differential protein interactions during development. We anticipate that this device will help expand the possible uses of C. elegans as a model organism, enabling its use in addressing fundamental questions at the subcellular scale, including the role of phase transitions in driving spatiotemporal intracellular organization within multicellular organisms.

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C. elegans Screen Identifies Autophagy Genes Specific to Multicellular Organisms

Cell ◽

10.1016/j.cell.2010.04.034 ◽

2010 ◽

Vol 141 (6) ◽

pp. 1042-1055 ◽

Cited By ~ 246

Author(s):

Ye Tian ◽

Zhipeng Li ◽

Wanqiu Hu ◽

Haiyan Ren ◽

E. Tian ◽

...

Keyword(s):

C Elegans ◽

Multicellular Organisms

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A genetic program mediates cold-warming response and promotes stress-induced phenoptosis in C. elegans

eLife ◽

10.7554/elife.35037 ◽

2018 ◽

Vol 7 ◽

Cited By ~ 6

Author(s):

Wei Jiang ◽

Yuehua Wei ◽

Yong Long ◽

Arthur Owen ◽

Bingying Wang ◽

...

Keyword(s):

Wild Population ◽

Molecular Genetic ◽

Genetic Program ◽

Transcriptional Program ◽

Uncharacterized Protein ◽

C Elegans ◽

Enhanced Resistance ◽

Hypothermic Stress ◽

Multicellular Organisms ◽

Encoding Genes

How multicellular organisms respond to and are impacted by severe hypothermic stress is largely unknown. From C. elegans screens for mutants abnormally responding to cold-warming stimuli, we identify a molecular genetic pathway comprising ISY-1, a conserved uncharacterized protein, and ZIP-10, a bZIP-type transcription factor. ISY-1 gatekeeps the ZIP-10 transcriptional program by regulating the microRNA mir-60. Downstream of ISY-1 and mir-60, zip-10 levels rapidly and specifically increase upon transient cold-warming exposure. Prolonged zip-10 up-regulation induces several protease-encoding genes and promotes stress-induced organismic death, or phenoptosis, of C. elegans. zip-10 deficiency confers enhanced resistance to prolonged cold-warming stress, more prominently in adults than larvae. We conclude that the ZIP-10 genetic program mediates cold-warming response and may have evolved to promote wild-population kin selection under resource-limiting and thermal stress conditions.

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let-7 controls the transition to adulthood by releasing select transcriptional regulators from repression by LIN41

10.1101/460352 ◽

2018 ◽

Cited By ~ 1

Author(s):

Florian Aeschimann ◽

Anca Neagu ◽

Magdalene Rausch ◽

Helge Großhans

Keyword(s):

Transition To Adulthood ◽

Progenitor Cell ◽

Temporal Patterning ◽

Cell Fates ◽

C Elegans ◽

Regulatory Module ◽

Single Target ◽

Dm Domain ◽

Multicellular Organisms ◽

Post Transcriptional Regulation

ABSTRACTDevelopment of multicellular organisms relies on faithful temporal control of cell fates. In Caenorhabditis elegans, the heterochronic pathway governs temporal patterning of somatic cells. This function may be phylogenetically conserved as several heterochronic genes have mammalian orthologues, and as the heterochronic let-7 miRNA and its regulator LIN28 appear to time the onset of puberty in mice and humans. Here, we have investigated how let-7 promotes the transition to adulthood in C. elegans. We find that let-7 controls each of three relevant processes, namely male and female sexual organ morphogenesis as well as changes in skin progenitor cell fates, through the same single target, lin-41. LIN41 in turn silences two pairs of targets post-transcriptionally, by binding and silencing their mRNAs. The EGR-type transcription factor LIN-29a and its co-factor, the NAB1/2 orthologous MAB-10, mediate control of progenitor cell fates and vulval integrity. By contrast, male tail development depends on regulation of the DM domain-containing transcription factors DMD-3 and MAB-3. Our results provide mechanistic insight into an exemplary temporal patterning pathway, demonstrate that let-7 – LIN41 function as a versatile regulatory module that can be connected to different outputs, and reveal how several levels of post-transcriptional regulation ultimately achieve effects through controlling transcriptional outputs.

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