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Elegans wnt

Malgorzata 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...
September 26, 2016: Genetics
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...
2016: Nature Communications
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
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)...
July 29, 2016: Cell Death and Differentiation
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
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
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
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
Kapil Dev Singh, Bernd Roschitzki, L Basten Snoek, Jonas Grossmann, Xue Zheng, Mark Elvin, Polina Kamkina, Sabine P Schrimpf, Gino B Poulin, Jan E Kammenga, Michael O Hengartner
Complex traits, including common disease-related traits, are affected by many different genes that function in multiple pathways and networks. The apoptosis, MAPK, Notch, and Wnt signalling pathways play important roles in development and disease progression. At the moment we have a poor understanding of how allelic variation affects gene expression in these pathways at the level of translation. Here we report the effect of natural genetic variation on transcript and protein abundance involved in developmental signalling pathways in Caenorhabditis elegans...
2016: PloS One
Maxime J Kinet, Jennifer A Malin, Mary C Abraham, Elyse S Blum, Melanie R Silverman, Yun Lu, Shai Shaham
Apoptosis is a prominent metazoan cell death form. Yet, mutations in apoptosis regulators cause only minor defects in vertebrate development, suggesting that another developmental cell death mechanism exists. While some non-apoptotic programs have been molecularly characterized, none appear to control developmental cell culling. Linker-cell-type death (LCD) is a morphologically conserved non-apoptotic cell death process operating in Caenorhabditis elegans and vertebrate development, and is therefore a compelling candidate process complementing apoptosis...
2016: ELife
Vincent Bertrand
The Wnt/β-catenin pathway plays key roles during animal development. In several species, β-catenin is used in a reiterative manner to regulate cell fate diversification between daughter cells following division. This binary cell fate specification mechanism has been observed in animals that belong to very diverse phyla: the nematode Caenorhabditis elegans, the annelid Platynereis, and the ascidian Ciona. It may also play a role in the regulation of several stem cell lineages in vertebrates. While the molecular mechanism behind this binary cell fate switch is not fully understood, it appears that both secreted Wnt ligands and asymmetric cortical factors contribute to the generation of the difference in nuclear β-catenin levels between daughter cells...
May 2016: Wiley Interdisciplinary Reviews. Developmental Biology
Lorenzo Rella, Euclides E Fernandes Póvoa, Hendrik C Korswagen
During development, cell migration plays a central role in the formation of tissues and organs. Understanding the molecular mechanisms that drive and control these migrations is a key challenge in developmental biology that will provide important insights into disease processes, including cancer cell metastasis. In this article, we discuss the Caenorhabditis elegans Q neuroblasts and their descendants as a tool to study cell migration at single-cell resolution in vivo. The highly stereotypical migration of these cells provides a powerful system to study the dynamic cytoskeletal processes that drive migration as well as the evolutionarily conserved signaling pathways (including different Wnt signaling cascades) that guide the cells along their specific trajectories...
April 2016: Genesis: the Journal of Genetics and Development
Matthew P Josephson, Yongping Chai, Guangshuo Ou, Erik A Lundquist
Directed neuroblast and neuronal migration is important in the proper development of nervous systems. In C. elegans the bilateral Q neuroblasts QR (on the right) and QL (on the left) undergo an identical pattern of cell division and differentiation but migrate in opposite directions (QR and descendants anteriorly and QL and descendants posteriorly). EGL-20/Wnt, via canonical Wnt signaling, drives the expression of MAB-5/Hox in QL but not QR. MAB-5 acts as a determinant of posterior migration, and mab-5 and egl-20 mutants display anterior QL descendant migrations...
2016: PloS One
Austin T Baldwin, Amy M Clemons, Bryan T Phillips
The Wnt/β-catenin signaling pathway is utilized across metazoans. However, the mechanism of signal transduction, especially dissociation of the β-catenin destruction complex by Dishevelled proteins, remains controversial. Here, we describe the function of the Dishevelled paralogs DSH-2 and MIG-5 in the Wnt/β-catenin asymmetry (WβA) pathway in Caenorhabditis elegans, where WβA drives asymmetric cell divisions throughout development. We find that DSH-2 and MIG-5 redundantly regulate cell fate in hypodermal seam cells...
March 1, 2016: Journal of Cell Science
Yuki Niwa, Takehiro Suzuki, Naoshi Dohmae, Siro Simizu
R-spondin1 (Rspo1) is a secreted protein that enhances Wnt signaling, which has crucial functions in embryonic development and several cancers. C-mannosylation is a rare type of glycosylation and might regulate secretion, protein-protein interactions, and enzymatic activity. Although human Rspo1 contains 2 predicted C-mannosylation sites, C-mannosylation of Rspo1 has not been reported, nor have its functional effects on this protein. In this study, we demonstrate by mass spectrometry that Rspo1 is C-mannosylated at W(153) and W(156)...
March 1, 2016: Molecular Biology of the Cell
Xiao-Tai Huang, Yuan Zhu, Leanne Lai Hang Chan, Zhongying Zhao, Hong Yan
In Caenorhabditis elegans, a large number of protein-protein interactions (PPIs) are identified by different experiments. However, a comprehensive weighted PPI network, which is essential for signaling pathway inference, is not yet available in this model organism. Therefore, we firstly construct an integrative PPI network in C. elegans with 12,951 interactions involving 5039 proteins from seven molecular interaction databases. Then, a reliability score based on a probabilistic graphical model (RSPGM) is proposed to assess PPIs...
January 2016: Molecular BioSystems
Amanda L Zacharias, Travis Walton, Elicia Preston, John Isaac Murray
The Wnt signaling pathway plays a conserved role during animal development in transcriptional regulation of distinct targets in different developmental contexts but it remains unclear whether quantitative differences in the nuclear localization of effector proteins TCF and β-catenin contribute to context-specific regulation. We investigated this question in Caenorhabditis elegans embryos by quantifying nuclear localization of fluorescently tagged SYS-1/β-catenin and POP-1/TCF and expression of Wnt ligands at cellular resolution by time-lapse microscopy and automated lineage tracing...
October 2015: PLoS Genetics
Chaogu Zheng, Margarete Diaz-Cuadros, Martin Chalfie
Wnt proteins regulate axonal outgrowth along the anterior-posterior axis, but the intracellular mechanisms that modulate the strength of Wnt signaling in axon guidance are largely unknown. Using the Caenorhabditis elegans mechanosensory PLM neurons, we found that posteriorly enriched LIN-44/Wnt acts as a repellent to promote anteriorly directed neurite outgrowth through the LIN-17/Frizzled receptor, instead of controlling neuronal polarity as previously thought. Dishevelled (Dsh) proteins DSH-1 and MIG-5 redundantly mediate the repulsive activity of the Wnt signals to induce anterior outgrowth, whereas DSH-1 also provides feedback inhibition to attenuate the signaling to allow posterior outgrowth against the Wnt gradient...
October 27, 2015: Proceedings of the National Academy of Sciences of the United States of America
Lakshmi Gorrepati, David M Eisenmann
In metazoans, stem cells in developing and adult tissues can divide asymmetrically to give rise to a daughter that differentiates and a daughter that retains the progenitor fate. Although the short-lived nematode C. elegans does not possess adult somatic stem cells, the lateral hypodermal seam cells behave in a similar manner: they divide once per larval stage to generate an anterior daughter that adopts a non-dividing differentiated fate and a posterior daughter that retains the seam fate and the ability to divide further...
January 2015: Worm
Mark Gurling, Gian Garriga
The C. elegans Q lineage provides a unique context for studying how cells divide asymmetrically to generate cells fated to die. The Q cell divides to form the Q.a and Q.p neuroblasts, each of which divides to produce neurons and a cell that dies by apoptosis; however, these neuroblasts employ different mechanisms to divide asymmetrically.(1) We discovered 2 distinct roles for TOE-2, a protein previously shown to be a target of the C. elegans ERK ortholog MPK-1, in promoting apoptosis in each of these neuroblast divisions...
January 2015: Worm
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