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Physiological Role of β-Catenin/TCF Signaling in Neurons of the Adult Brain

Neurochemical Research

Springer US

Wnt, LEF1/TCF, Brain, Neurogenesis, NMDA, Thalamus

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      Abstract

      Wnt/β-catenin pathway, the effectors of which are transcription factors of the LEF1/TCF family, is primarily associated with development. Strikingly, however, some of the genes of the pathway are schizophrenia susceptibility genes, and the proteins that are often mutated in neurodegenerative diseases have the ability to regulate β-catenin levels. If impairment of this pathway indeed leads to these pathologies, then it likely plays a physiological role in the adult brain. This review provides an overview of the current knowledge on this subject. The involvement of β-catenin and LEF1/TCF factors in adult neurogenesis, synaptic plasticity, and the function of thalamic neurons are discussed. The data are still very preliminary and often based on circumstantial or indirect evidence. Further research might help to understand the etiology of the aforementioned pathologies.

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      Wnt/β-catenin signaling and disease.

      The WNT signal transduction cascade controls myriad biological phenomena throughout development and adult life of all animals. In parallel, aberrant Wnt signaling underlies a wide range of pathologies in humans. In this Review, we provide an update of the core Wnt/β-catenin signaling pathway, discuss how its various components contribute to disease, and pose outstanding questions to be addressed in the future. Copyright © 2012 Elsevier Inc. All rights reserved.
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        The many faces and functions of β-catenin.

        β-Catenin (Armadillo in Drosophila) is a multitasking and evolutionary conserved molecule that in metazoans exerts a crucial role in a multitude of developmental and homeostatic processes. More specifically, β-catenin is an integral structural component of cadherin-based adherens junctions, and the key nuclear effector of canonical Wnt signalling in the nucleus. Imbalance in the structural and signalling properties of β-catenin often results in disease and deregulated growth connected to cancer and metastasis. Intense research into the life of β-catenin has revealed a complex picture. Here, we try to capture the state of the art: we try to summarize and make some sense of the processes that regulate β-catenin, as well as the plethora of β-catenin binding partners. One focus will be the interaction of β-catenin with different transcription factors and the potential implications of these interactions for direct cross-talk between β-catenin and non-Wnt signalling pathways.
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          Wnt signalling regulates adult hippocampal neurogenesis.

          The generation of new neurons from neural stem cells is restricted to two regions of the adult mammalian central nervous system: the subventricular zone of the lateral ventricle, and the subgranular zone of the hippocampal dentate gyrus. In both regions, signals provided by the microenvironment regulate the maintenance, proliferation and neuronal fate commitment of the local stem cell population. The identity of these signals is largely unknown. Here we show that adult hippocampal stem/progenitor cells (AHPs) express receptors and signalling components for Wnt proteins, which are key regulators of neural stem cell behaviour in embryonic development. We also show that the Wnt/beta-catenin pathway is active and that Wnt3 is expressed in the hippocampal neurogenic niche. Overexpression of Wnt3 is sufficient to increase neurogenesis from AHPs in vitro and in vivo. By contrast, blockade of Wnt signalling reduces neurogenesis from AHPs in vitro and abolishes neurogenesis almost completely in vivo. Our data show that Wnt signalling is a principal regulator of adult hippocampal neurogenesis and provide evidence that Wnt proteins have a role in adult hippocampal function.
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            Author and article information

            Affiliations
            [ ]Laboratory of Neurodegeneration, International Institute of Molecular and Cell Biology, ul. Ks. Trojdena 4, 02-109 Warsaw, Poland
            [ ]Centre of New Technologies, University of Warsaw, Zwirki i Wigury 93, 02-089 Warsaw, Poland
            Contributors
            +48-22-5970763 , +48-22-5540800 , +48-22-5970715 , +48-22-5540041 , mwisniew@iimcb.gov.pl , m.wisniewska@cent.uw.edu.pl
            Journal
            Neurochem Res
            Neurochem. Res
            Neurochemical Research
            Springer US (Boston )
            0364-3190
            1573-6903
            2 February 2013
            2 February 2013
            June 2013
            : 38
            : 6
            : 1144-1155
            23377854
            3653035
            980
            10.1007/s11064-013-0980-9
            © The Author(s) 2013

            Open AccessThis article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

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            © Springer Science+Business Media New York 2013

            Neurosciences

            thalamus, nmda, neurogenesis, brain, lef1/tcf, wnt

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