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Elegans wnt

Alexey Moskalev, Mikhail Shaposhnikov, Nadezhda Zemskaya, Alexey Belyi, Eugenia Dobrovolskaya, Anna Patova, Zulfiya Guvatova, Elena Lukyanova, Anastasiya Snezhkina, Anna Kudryavtseva
BACKGROUND: We have previously showed that the carotenoid fucoxanthin can increase the lifespan in Drosophila melanogaster and Caenorhabditis elegans. However, the molecular mechanisms of the geroprotective effect of fucoxanthin have not been studied so far. RESULTS: Here, we studied the effects of fucoxanthin on the Drosophila aging process at the molecular and the whole organism levels. At the organismal level, fucoxanthin increased the median lifespan and had a positive effect on fecundity, fertility, intestinal barrier function, and nighttime sleep...
February 9, 2018: BMC Genomics
Jiaming Wang, Mei Ding
Growing axons are exposed to various guidance cues en route to their targets, but the mechanisms that govern the response of growth cones to combinations of signals remain largely elusive. Here, we found that the sole Robo receptor, SAX-3, in Caenorhabditis elegans functions as a coreceptor for Wnt/CWN-2 molecules. SAX-3 binds to Wnt/CWN-2 and facilitates the membrane recruitment of CWN-2. SAX-3 forms a complex with the Ror/CAM-1 receptor and its downstream effector Dsh/DSH-1, promoting signal transduction from Wnt to Dsh...
February 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
Guillaume Bordet, Vincent Bertrand
Transcription factors of the Zic family play important roles during animal development, and their misregulation has been implicated in several human diseases. Zic proteins are present in nematodes, and their function has been mostly studied in the model organism C. elegans. C. elegans possesses only one Zic family member, REF-2. Functional studies have shown that this factor plays a key role during the development of the nervous system, epidermis, and excretory system. In addition, they have revealed that the C...
2018: Advances in Experimental Medicine and Biology
Kenji Sugioka, Lars-Eric Fielmich, Kota Mizumoto, Bruce Bowerman, Sander van den Heuvel, Akatsuki Kimura, Hitoshi Sawa
The adenomatous polyposis coli (APC) tumor suppressor has dual functions in Wnt/β-catenin signaling and accurate chromosome segregation and is frequently mutated in colorectal cancers. Although APC contributes to proper cell division, the underlying mechanisms remain poorly understood. Here we show that Caenorhabditis elegans APR-1/APC is an attenuator of the pulling forces acting on the mitotic spindle. During asymmetric cell division of the C. elegans zygote, a LIN-5/NuMA protein complex localizes dynein to the cell cortex to generate pulling forces on astral microtubules that position the mitotic spindle...
January 18, 2018: Proceedings of the National Academy of Sciences of the United States of America
Jennifer K Heppert, Ariel M Pani, Allyson M Roberts, Daniel J Dickinson, Bob Goldstein
Oriented cell divisions are critical to establish and maintain cell fates and tissue organization. Diverse extracellular and intracellular cues have been shown to provide spatial information for mitotic spindle positioning, however, the molecular mechanisms by which extracellular signals communicate with cells to direct mitotic spindle positioning are largely unknown. In animal cells, oriented cell divisions are often achieved by the localization of force-generating, motor protein complexes to discrete cortical domains...
January 18, 2018: Genetics
Neide Vieira, Carlos Bessa, Ana J Rodrigues, Paulo Marques, Fung-Yi Chan, Ana Xavier de Carvalho, Margarida Correia-Neves, Nuno Sousa
The sorting nexins family of proteins (SNXs) plays pleiotropic functions in protein trafficking and intracellular signaling and has been associated with several disorders, namely Alzheimer's disease and Down's syndrome. Despite the growing association of SNXs with neurodegeneration, not much is known about their function in the nervous system. The aim of this work was to use the nematode Caenorhabditis elegans that encodes in its genome eight SNXs orthologs, to dissect the role of distinct SNXs, particularly in the nervous system...
December 1, 2017: Cellular and Molecular Life Sciences: CMLS
Dimitris Katsanos, Sneha L Koneru, Lamia Mestek Boukhibar, Nicola Gritti, Ritobrata Ghose, Peter J Appleford, Maria Doitsidou, Alison Woollard, Jeroen S van Zon, Richard J Poole, Michalis Barkoulas
Biological systems are subject to inherent stochasticity. Nevertheless, development is remarkably robust, ensuring the consistency of key phenotypic traits such as correct cell numbers in a certain tissue. It is currently unclear which genes modulate phenotypic variability, what their relationship is to core components of developmental gene networks, and what is the developmental basis of variable phenotypes. Here, we start addressing these questions using the robust number of Caenorhabditis elegans epidermal stem cells, known as seam cells, as a readout...
November 2017: PLoS Biology
Gerard Limerick, Xia Tang, Won Suk Lee, Ahmed Mohamed, Aseel Al-Aamiri, William G Wadsworth
Neurons extend processes that vary in number, length, and direction of outgrowth. Extracellular cues help determine outgrowth patterns. In Caenorhabditis elegans, neurons respond to the extracellular UNC-6 (netrin) cue via UNC-40 (DCC) and UNC-5 (UNC5) receptors. Previously we presented evidence that UNC-40 asymmetric localization at the plasma membrane is self-organizing and that UNC-40 can localize and mediate outgrowth at randomly selected sites. Here we provide further evidence for a statistically oriented asymmetric localization (SOAL) model in which UNC-5 receptor activity affects patterns of axon outgrowth by regulating UNC-40 asymmetric localization...
November 1, 2017: Genetics
Jason Chien, Ranjan Devkota, Nebeyu Yosef, Catarina Mörck
The Caenorhabditis elegans ventral nerve cord (VNC) consists of two asymmetric bundles of neurons and axons that are separated by the midline. How the axons are guided to stay on the correct sides of the midline remains poorly understood. Here we provide evidence that the conserved Wnt signaling pathway along with the Netrin and Robo pathways constitute a combinatorial code for midline guidance of PVP and PVQ axons that extend into the VNC. Combined loss of the Wnts CWN-1, CWN-2, and EGL-20 or loss of the Wnt receptor CAM-1 caused >70% of PVP and PVQ axons to inappropriately cross over from the left side to the right side...
December 2017: Genetics
Sertan Kutal Gokce, Evan Marley Hegarty, Sudip Mondal, Peisen Zhao, Navid Ghorashian, Massimo A Hilliard, Adela Ben-Yakar
Several sophisticated microfluidic devices have recently been proposed for femtosecond laser axotomy in the nematode C. elegans for immobilization of the animals for surgery to overcome time-consuming and labor-intensive manual processes. However, nerve regeneration studies require long-term recovery of the animals and multiple imaging sessions to observe the regeneration capabilities of their axons post-injury. Here we present a simple, multi-trap device, consisting of a single PDMS (polydimethylsiloxane) layer, which can immobilize up to 20 animals at the favorable orientation for optical access needed for precise laser surgery and high-resolution imaging...
August 29, 2017: Scientific Reports
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...
October 1, 2017: Developmental Biology
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
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...
June 2017: Nanotoxicology
Kristian Saied-Santiago, Robert A Townley, John D Attonito, Dayse S da Cunha, Carlos A Díaz-Balzac, Eillen Tecle, Hannes E Bülow
Heparan sulfates (HS) 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 cofactors 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...
August 2017: Genetics
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 elucidate 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 Wnt receptor, ROR receptor tyrosine kinase (RTK), CAM-1, which functions in postsynaptic body-wall muscles...
July 2017: Genetics
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
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
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
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
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
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