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      Primary cilia in rat mature Müller glia: downregulation of IFT20 expression reduces sonic hedgehog-mediated proliferation and dedifferentiation potential of Müller glia primary cultures.

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          Abstract

          Primary cilia are specialized organelles that extend from the cell surface and concentrate signal transduction components. In the nervous system, primary cilia-associated signals, such as sonic hedgehog (Shh), regulate cell proliferation and neuronal fate. Primary cilia assembly and maintenance require a multi-subunit intraflagellar transport (IFT) protein complex. Defects in primary cilia and IFT proteins are associated to severe pathological phenotypes. In the retina, the study of primary cilia has been mainly restricted to the specialized photoreceptor outer segment. The presence and physiological role of primary cilia in other retinal cells have not been clearly elucidated. Müller cells are the main glia of the retina where they exert distinct functions to maintain homeostasis. In pathological conditions, Müller cells mount a unique regenerative response through the processes of dedifferentiation, proliferation, and differentiation into neuronal lineages. The involvement of IFT proteins or a primary cilium in these processes has not been explored. In this study, we used mature Müller glia primary cultures to reveal the presence of the primary cilia by immunoreactivity to acetylated α-tubulin and γ-tubulin, which localize to the axoneme and ciliar basal body, respectively. We demonstrate that si-RNA-mediated downregulation of IFT20 gene expression, a main component of the IFT machinery, blocks Shh-induced Müller cell proliferation. We present evidence that IFT20 ablation impairs the dedifferentiation capacity of Müller cells induced by Shh and by glutamate. Our demonstration that Müller glia expresses IFT20 and harbors primary cilia, and opens new venues of research on the role of primary cilia in the retina.

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          Author and article information

          Journal
          Cell. Mol. Neurobiol.
          Cellular and molecular neurobiology
          Springer Nature America, Inc
          1573-6830
          0272-4340
          May 2015
          : 35
          : 4
          Affiliations
          [1 ] Departamento de Farmacobiología, CINVESTAV Sede Sur, Calzada de los Tenorios 235, Mexico, DF, Mexico.
          Article
          10.1007/s10571-014-0149-3
          25504432
          42ea3a38-381f-4f48-8fbb-ca35f6326eed
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