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      Involvement of YAP-1, the Homolog of Yes-Associated Protein, in the Wnt-Mediated Neuronal Polarization in Caenorhabditis elegans

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          Abstract

          Guidance molecules, receptors, and downstream signaling pathways involved in the asymmetric neuronal cell migration and process outgrowth have been identified from genetic studies using model organisms, most of which are evolutionarily conserved. In the nematode Caenorhabditis elegans, the roles of Wnt ligands and their receptors in the polarization of specific sets of neurons along the anterior-posterior (A-P) body axis have been well elucidated, but their downstream effectors are relatively unknown. Here, we report yap-1 , encoding an evolutionarily conserved transcriptional co-activator, as a novel player in the Wnt-mediated asymmetric development of specific neurons in C. elegans. We found that the loss of yap-1 activity failed to restrict the dendritic extension of ALM neurons to the anterior orientation, which is similar to the phenotype caused by defective cwn-1 and cwn-2 Wnt gene activities. Cell-specific rescue experiments showed that yap-1 acts in the cell autonomous manner to polarize ALM dendrites. We also found that subcellular localization of YAP-1 was spatio-temporally regulated. The loss of yap-1 in Wnt-deficient mutants did not increase the severity of the ALM polarity defect of the mutants. Wnt-deficient animals displayed abnormal subcellular localization of YAP-1 in touch receptor neurons, suggesting that yap-1 may act downstream of the cwn-1/ cwn-2 Wnt ligands for the ALM polarization process. Together, we have identified a new role for YAP-1 in neuronal development and our works will contribute to further understanding of intracellular events in neuronal polarization during animal development.

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          Most cited references 40

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          The genetics of Caenorhabditis elegans.

          Methods are described for the isolation, complementation and mapping of mutants of Caenorhabditis elegans, a small free-living nematode worm. About 300 EMS-induced mutants affecting behavior and morphology have been characterized and about one hundred genes have been defined. Mutations in 77 of these alter the movement of the animal. Estimates of the induced mutation frequency of both the visible mutants and X chromosome lethals suggests that, just as in Drosophila, the genetic units in C. elegans are large.
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            The hippo signaling pathway in development and cancer.

             Duojia Pan (2010)
            First discovered in Drosophila, the Hippo signaling pathway is a conserved regulator of organ size. Central to this pathway is a kinase cascade leading from the tumor suppressor Hippo (Mst1 and Mst2 in mammals) to the oncoprotein Yki (YAP and TAZ in mammals), a transcriptional coactivator of target genes involved in cell proliferation and survival. Here, I review recent progress in elucidating the molecular mechanism and physiological function of Hippo signaling in Drosophila and mammals. These studies suggest that the core Hippo kinase cascade integrates multiple upstream inputs, enabling dynamic regulation of tissue homeostasis in animal development and physiology. Copyright © 2010 Elsevier Inc. All rights reserved.
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              The nuts and bolts of AGC protein kinases.

              The AGC kinase subfamily of protein kinases contains 60 members, including PKA, PKG and PKC. The family comprises some intensely examined protein kinases (such as Akt, S6K, RSK, MSK, PDK1 and GRK) as well as many less well-studied enzymes (such as SGK, NDR, LATS, CRIK, SGK494, PRKX, PRKY and MAST). Research has shed new light onto the architecture and regulatory mechanisms of these kinases. In addition, AGC kinases mediate diverse and important cellular functions, and their mutation and/or dysregulation contributes to the pathogenesis of many human diseases, including cancer and diabetes.
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                Author and article information

                Journal
                G3 (Bethesda)
                Genetics
                G3: Genes, Genomes, Genetics
                G3: Genes, Genomes, Genetics
                G3: Genes, Genomes, Genetics
                G3: Genes|Genomes|Genetics
                Genetics Society of America
                2160-1836
                31 May 2018
                August 2018
                : 8
                : 8
                : 2595-2602
                Affiliations
                Department of Biological Sciences, Institute of Molecular Biology and Genetics, Seoul National University, Gwanak-ro 1, Gwanak-gu, Seoul, Korea 08826
                Author notes
                [1]

                Present address: Department of Cell and Regenerative Biology, University of Wisconsin-Madison, Madison, WI53705, U.S.A.

                [2 ]Correspondences to: Junho Lee, Department of Biological Sciences, Seoul National University, Gwanak-ro 1, Gwanak-gu, Seoul, Korea 08826, elegans@ 123456snu.ac.kr
                Article
                GGG_200325
                10.1534/g3.118.200325
                6071598
                29853655
                Copyright © 2018 Lee et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Page count
                Figures: 5, Tables: 0, Equations: 0, References: 40, Pages: 8
                Product
                Categories
                Investigations

                Genetics

                the wnt pathway, c. elegans, neuronal asymmetry, development, yap-1

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