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https://www.readbyqxmd.com/read/28694018/the-enu-3-protein-family-members-function-in-the-wnt-pathway-parallel-to-unc-6-netrin-to-promote-motor-neuron-axon-outgrowth-in-c-elegans
#1
Roxana Oriana Florica, Victoria Hipolito, Stephen Bautista, Homa Anvari, Chloe Rapp, Suzan El-Rass, Alimohammad Asgharian, Costin N Antonescu, Marie T Killeen
The axons of the DA and DB classes of motor neurons fail to reach the dorsal cord in the absence of the guidance cue UNC-6/Netrin or its receptor UNC-5 in C. elegans. However, the axonal processes usually exit their cell bodies in the ventral cord in the absence of both molecules. Strains lacking functional versions of UNC-6 or UNC-5 have a low level of DA and DB motor neuron axon outgrowth defects. We found that mutations in the genes for all six of the ENU-3 proteins function to enhance the outgrowth defects of the DA and DB axons in strains lacking either UNC-6 or UNC-5...
July 7, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28674811/a-phenotype-based-rnai-screening-for-ras-erk-mapk-signaling-associated-stem-cell-regulators-in-c-elegans
#2
Myon-Hee Lee, Dong Suk Yoon
Stem cells have the ability to self-renew and to generate differentiated cell types. A regulatory network that controls this balance is critical for stem cell homeostasis and normal animal development. Particularly, Ras-ERK/MAPK signaling pathway is critical for stem cell self-renewal and differentiation in mammals, including humans. Aberrant regulation of Ras-ERK/MAPK signaling pathway results in either stem cell or overproliferation. Therefore, the identification of Ras-ERK/MAPK signaling pathway-associated regulators is critical to understand the mechanism of stem cell (possibly cancer stem cell) control...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28673184/toxicogenomics-of-iron-oxide-nanoparticles-in-the-nematode-c-elegans
#3
Laura Gonzalez-Moragas, Si-Ming Yu, Núria Benseny-Cases, Stephen Stürzenbaum, Anna Roig, Anna Laromaine
We present a mechanistic study of the effect of iron oxide nanoparticles (SPIONs) in Caenorhabditis elegans combining a genome-wide analysis with the investigation of specific molecular markers frequently linked to nanotoxicity. The effects of two different coatings were explored: citrate, an anionic stabilizer, and bovine serum albumin, as a pre-formed protein corona. The transcriptomic study identified differentially expressed genes following an exposure to SPIONs. The expression of genes involved in oxidative stress, metal detoxification response, endocytosis, intestinal integrity and iron homeostasis was quantitatively evaluated...
July 4, 2017: Nanotoxicology
https://www.readbyqxmd.com/read/28576860/coordination-of-heparan-sulfate-proteoglycans-with-wnt-signaling-to-control-cellular-migrations-and-positioning-in-caenorhabditis-elegans
#4
Kristian Saied-Santiago, Robert A Townley, John D Attonito, Dayse S da Cunha, Carlos A Diaz-Balzac, Eillen Tecle, Hannes E Bülow
Heparan sulfates are linear polysaccharides with complex modification patterns, which are covalently bound via conserved attachment sites to core proteins to form heparan sulfate proteoglycans (HSPGs). HSPGs regulate many aspects of the development and function of the nervous system, including cell migration, morphology, and network connectivity. HSPGs function as co-factors for multiple signaling pathways, including the Wnt signaling molecules and their Frizzled receptors. To investigate the functional interactions among the HSPG and Wnt networks, we conducted genetic analyses of each, and also between these networks using five cellular migrations in the nematode Caenorhabditis elegans We find that HSPG core proteins act genetically in a combinatorial fashion dependent on the cellular contexts...
June 2, 2017: Genetics
https://www.readbyqxmd.com/read/28515212/regulation-of-wnt-signaling-at-the-neuromuscular-junction-by-the-immunoglobulin-superfamily-protein-rig-3-in-caenorhabditis-elegans
#5
Pratima Pandey, Ashwani Bhardwaj, Kavita Babu
Perturbations in synaptic function could affect the normal behavior of an animal, making it important to understand the regulatory mechanisms of synaptic signaling. Previous work has shown that in Caenorhabditis elegans an immunoglobulin superfamily protein, RIG-3, functions in presynaptic neurons to maintain normal acetylcholine receptor levels at the neuromuscular junction (NMJ). In this study, we elucidated the molecular and functional mechanism of RIG-3 We demonstrate by genetic and BiFC (Bi-molecular Fluorescence Complementation) assays that presynaptic RIG-3 functions by directly interacting with the immunoglobulin domain of the nonconventional-conventional Wnt receptor, ROR receptor tyrosine kinase (RTK), CAM-1, which functions in postsynaptic body-wall muscles...
July 2017: Genetics
https://www.readbyqxmd.com/read/28409301/wnt-signaling-polarizes-c-elegans-asymmetric-cell-divisions-during-development
#6
Arielle Koonyee Lam, Bryan T Phillips
Asymmetric cell division is a common mode of cell differentiation during the invariant lineage of the nematode, C. elegans. Beginning at the four-cell stage, and continuing throughout embryogenesis and larval development, mother cells are polarized by Wnt ligands, causing an asymmetric inheritance of key members of a Wnt/β-catenin signal transduction pathway termed the Wnt/β-catenin asymmetry pathway. The resulting daughter cells are distinct at birth with one daughter cell activating Wnt target gene expression via β-catenin activation of TCF, while the other daughter displays transcriptional repression of these target genes...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/28384160/a-wnt-planar-polarity-pathway-instructs-neurite-branching-by-restricting-f-actin-assembly-through-endosomal-signaling
#7
Chun-Hao Chen, Chun-Wei He, Chien-Po Liao, Chun-Liang Pan
Spatial arrangement of neurite branching is instructed by both attractive and repulsive cues. Here we show that in C. elegans, the Wnt family of secreted glycoproteins specify neurite branching sites in the PLM mechanosensory neurons. Wnts function through MIG-1/Frizzled and the planar cell polarity protein (PCP) VANG-1/Strabismus/Vangl2 to restrict the formation of F-actin patches, which mark branching sites in nascent neurites. We find that VANG-1 promotes Wnt signaling by facilitating Frizzled endocytosis and genetically acts in a common pathway with arr-1/β-arrestin, whose mutation results in defective PLM branching and F-actin patterns similar to those in the Wnt, mig-1 or vang-1 mutants...
April 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28114100/the-genetics-of-axon-guidance-and-axon-regeneration-in-caenorhabditis-elegans
#8
REVIEW
Andrew D Chisholm, Harald Hutter, Yishi Jin, William G Wadsworth
The correct wiring of neuronal circuits depends on outgrowth and guidance of neuronal processes during development. In the past two decades, great progress has been made in understanding the molecular basis of axon outgrowth and guidance. Genetic analysis in Caenorhabditis elegans has played a key role in elucidating conserved pathways regulating axon guidance, including Netrin signaling, the slit Slit/Robo pathway, Wnt signaling, and others. Axon guidance factors were first identified by screens for mutations affecting animal behavior, and by direct visual screens for axon guidance defects...
November 2016: Genetics
https://www.readbyqxmd.com/read/28098310/a-computational-model-predicts-genetic-nodes-that-allow-switching-between-species-specific-responses-in-a-conserved-signaling-network
#9
Adriana T Dawes, David Wu, Karley K Mahalak, Edward M Zitnik, Natalia Kravtsova, Haiwei Su, Helen M Chamberlin
Cell signaling networks regulate a variety of developmental and physiological processes, and changes in their response to external stimuli are often implicated in disease initiation and progression. To elucidate how different responses can arise from conserved signaling networks, we have developed a mathematical model of the well-characterized Caenorhabditis vulval development network involving EGF, Wnt and Notch signaling that recapitulates biologically observed behaviors. We experimentally block a specific element of the EGF pathway (MEK), and find different behaviors in vulval development in two Caenorhabditis species, C...
February 20, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/28049659/reciprocal-signaling-by-wnt-and-notch-specifies-a-muscle-precursor-in-the-c-elegans-embryo
#10
Scott M Robertson, Jessica Medina, Marieke Oldenbroek, Rueyling Lin
The MS blastomere produces one-third of the body wall muscles (BWMs) in the C. elegans embryo. MS-derived BWMs require two distinct cell-cell interactions, the first inhibitory and the second, two cell cycles later, required to overcome this inhibition. The inductive interaction is not required if the inhibitory signal is absent. Although the Notch receptor GLP-1 was implicated in both interactions, the molecular nature of the two signals was unknown. We now show that zygotically expressed MOM-2 (Wnt) is responsible for both interactions...
February 1, 2017: Development
https://www.readbyqxmd.com/read/27958363/wnt-ligands-differentially-regulate-toxicity-and-translocation-of-graphene-oxide-through-different-mechanisms-in-caenorhabditis-elegans
#11
Lingtong Zhi, Mingxia Ren, Man Qu, Hanyu Zhang, Dayong Wang
In this study, we investigated the possible involvement of Wnt signals in the control of graphene oxide (GO) toxicity using the in vivo assay system of Caenorhabditis elegans. In nematodes, the Wnt ligands, CWN-1, CWN-2, and LIN-44, were found to be involved in the control of GO toxicity. Mutation of cwn-1 or lin-44 gene induced a resistant property to GO toxicity and resulted in the decreased accumulation of GO in the body of nematodes, whereas mutation of cwn-2 gene induces a susceptible property to GO toxicity and an enhanced accumulation of GO in the body of nematodes...
December 13, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27901397/a-systems-toxicology-approach-reveals-the-wnt-mapk-crosstalk-pathway-mediated-reproductive-failure-in-caenorhabditis-elegans-exposed-to-graphene-oxide-go-but-not-to-reduced-graphene-oxide-rgo
#12
Nivedita Chatterjee, Youngho Kim, Jisu Yang, Carlos P Roca, Sang-Woo Joo, Jinhee Choi
The potential hazards of graphene nanomaterials were investigated by exposing the nematode Caenorhabditis elegans to graphene oxide (GO) and reduced graphene oxide (rGO). The underlying mechanisms of the nano-bio interaction were addressed with an integrated systems toxicology approach using global transcriptomics, network-based pathway analysis, and experimental validation of the in-silico-derived hypotheses. Graphene oxide was found to reduce the worms' reproductive health to a greater degree than rGO, but it did not affect survival (24 h endpoint)...
February 2017: Nanotoxicology
https://www.readbyqxmd.com/read/27672093/mitotic-spindle-positioning-in-the-ems-cell-of-caenorhabditis-elegans-requires-let-99-and-lin-5-numa
#13
Małgorzata J Liro, Lesilee S Rose
Asymmetric divisions produce daughter cells with different fates, and thus are critical for animal development. During asymmetric divisions, the mitotic spindle must be positioned on a polarized axis to ensure the differential segregation of cell fate determinants into the daughter cells. In many cell types, a cortically localized complex consisting of Gα, GPR-1/2, and LIN-5 (Gαi/Pins/Mud, Gαi/LGN/NuMA) mediates the recruitment of dynactin/dynein, which exerts pulling forces on astral microtubules to physically position the spindle...
November 2016: Genetics
https://www.readbyqxmd.com/read/27561390/the-tumour-suppressor-cyld-regulates-the-p53-dna-damage-response
#14
Vanesa Fernández-Majada, Patrick-Simon Welz, Maria A Ermolaeva, Michael Schell, Alexander Adam, Felix Dietlein, David Komander, Reinhard Büttner, Roman K Thomas, Björn Schumacher, Manolis Pasparakis
The tumour suppressor CYLD is a deubiquitinase previously shown to inhibit NF-κB, MAP kinase and Wnt signalling. However, the tumour suppressing mechanisms of CYLD remain poorly understood. Here we show that loss of CYLD catalytic activity causes impaired DNA damage-induced p53 stabilization and activation in epithelial cells and sensitizes mice to chemical carcinogen-induced intestinal and skin tumorigenesis. Mechanistically, CYLD interacts with and deubiquitinates p53 facilitating its stabilization in response to genotoxic stress...
August 26, 2016: Nature Communications
https://www.readbyqxmd.com/read/27527215/the-role-of-the-c-clamp-in-wnt-related-colorectal-cancers
#15
REVIEW
Aditi J Ravindranath, Ken M Cadigan
T-cell Factor/Lymphoid Enhancer Factor (TCF/LEF) transcription factors are major regulators of Wnt targets, and the products of the TCF7 and TCF7L2 genes have both been implicated in the progression of colorectal cancer in animal models and humans. TCFs recognize specific DNA sequences through their high mobility group (HMG) domains, but invertebrate TCFs and some isoforms of vertebrate TCF7 and TCF7L2 contain a second DNA binding domain known as the C-clamp. This review will cover the basic properties of C-clamps and their importance in Wnt signaling, using data from Drosophila, C...
2016: Cancers
https://www.readbyqxmd.com/read/27472063/transcriptional-control-of-non-apoptotic-developmental-cell-death-in-c-elegans
#16
Jennifer A Malin, Maxime J Kinet, Mary C Abraham, Elyse S Blum, Shai Shaham
Programmed cell death is an essential aspect of animal development. Mutations in vertebrate genes that mediate apoptosis only mildly perturb development, suggesting that other cell death modes likely have important roles. Linker cell-type death (LCD) is a morphologically conserved cell death form operating during the development of Caenorhabditis elegans and vertebrates. We recently described a molecular network governing LCD in C. elegans, delineating a key role for the transcription factor heat-shock factor 1 (HSF-1)...
December 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27462437/a-novel-role-for-the-tumour-suppressor-nitrilase1-modulating-the-wnt-%C3%AE-catenin-signalling-pathway
#17
Sonnhild Mittag, Tomas Valenta, Jörg Weiske, Laura Bloch, Susanne Klingel, Dietmar Gradl, Franziska Wetzel, Yuan Chen, Iver Petersen, Konrad Basler, Otmar Huber
Nitrilase1 was classified as a tumour suppressor in association with the fragile histidine-triad protein Fhit. However, knowledge about nitrilase1 and its tumour suppressor function is still limited. Whereas nitrilase1 and Fhit are discrete proteins in mammals, they are merged in Drosophila melanogaster and Caenorhabditis elegans. According to the Rosetta-Stone hypothesis, proteins encoded as fusion proteins in one organism and as separate proteins in another organism may act in the same signalling pathway...
2016: Cell Discovery
https://www.readbyqxmd.com/read/27383912/the-adhesion-gpcr-latrophilin-a-novel-signaling-cascade-in-oriented-cell-division-and-anterior-posterior-polarity
#18
COMMENT
Jana Winkler, Simone Prömel
Although several signaling pathways in oriented cell division have been well characterized such as delta/notch inductions or wnt/frizzled-based anterior-posterior polarity, there is strong evidence for additional signal pathways controlling early anterior-posterior polarity decisions. The homolog of the adhesion G protein-coupled receptor latrophilin, LAT-1 has been identified as a receptor essential for oriented cell division in an anterior-posterior direction of specific blastomeres in the early C. elegans embryo...
April 2016: Worm
https://www.readbyqxmd.com/read/27123368/how-targets-select-activation-or-repression-in-response-to-wnt
#19
Sabrina Murgan, Vincent Bertrand
In metazoans, the Wnt signaling pathway plays a key role in the regulation of binary decisions during development. During this process different sets of target genes are activated in cells where the Wnt pathway is active (classic target genes) versus cells where the pathway is inactive (opposite target genes). While the mechanism of transcriptional activation is well understood for classic target genes, how opposite target genes are activated in the absence of Wnt remains poorly characterized. Here we discuss how the key transcriptional mediator of the Wnt pathway, the TCF family member POP-1, regulates opposite target genes during C...
October 2015: Worm
https://www.readbyqxmd.com/read/27073738/orchestrating-a-p-and-d-v-guidance-a-wnt-netrin-tale
#20
Naomi Levy-Strumpf
While ample information was gathered in identifying guidance cues and their downstream mediators, very little is known about how the information from multiple extracellular cues is intracellularly to generate normal patterning. Netrin and Wnt signaling pathways play key roles in normal development as well as in malignancies. In C. elegans, as in vertebrates, dorso-ventral (D/V) graded distributions of UNC-6/Netrin and antero-posterior (A/P) graded distributions of Wnts provide instructive polarity information to guide cells and axons along their respective gradients...
January 2016: Worm
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