P53 is required for the developmental restriction in Müller glial proliferation in mouse retina

Authors

  • Yumi Ueki,

    1. Department of Biological Structure, University of Washington, Seattle, Washington
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  • Mike O. Karl,

    1. Center for Regenerative Therapies Dresden, Technische Universität Dresden, Fetscherstraβe 105, Dresden, Germany
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  • Samuel Sudar,

    1. Department of Biological Structure, University of Washington, Seattle, Washington
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  • Julia Pollak,

    1. Department of Biological Structure, University of Washington, Seattle, Washington
    2. Neurobiology and Behavior Program, University of Washington, Seattle, Washington
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  • Russell J. Taylor,

    1. Department of Biological Structure, University of Washington, Seattle, Washington
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  • Kati Loeffler,

    1. Center for Regenerative Therapies Dresden, Technische Universität Dresden, Fetscherstraβe 105, Dresden, Germany
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  • Matthew S. Wilken,

    1. Department of Biological Structure, University of Washington, Seattle, Washington
    2. Molecular and Cellular Biology Program, University of Washington, Seattle, Washington
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  • Sara Reardon,

    1. Department of Biological Structure, University of Washington, Seattle, Washington
    2. Molecular and Cellular Biology Program, University of Washington, Seattle, Washington
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  • Thomas A. Reh

    Corresponding author
    1. Department of Biological Structure, University of Washington, Seattle, Washington
    2. Neurobiology and Behavior Program, University of Washington, Seattle, Washington
    3. Molecular and Cellular Biology Program, University of Washington, Seattle, Washington
    • Professor of Biological Structure Director, Neurobiology and Behavior, 357420 Health Sciences Center, University of Washington, School of Medicine, Seattle, WA 98195, USA
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Abstract

Müller glia are normally mitotically quiescent cells, but in certain pathological states they can re-enter the mitotic cell cycle. While several cell cycle regulators have been shown to be important in this process, a role for the tumor suppressor, p53, has not been demonstrated. Here, we investigated a role for p53 in limiting the ability of Müller glia to proliferate in the mature mouse retina. Our data demonstrate that Müller glia undergo a developmental restriction in their potential to proliferate. Retinal explants or dissociated cultures treated with EGF become mitotically quiescent by the end of the second postnatal week. In contrast, Müller glia from adult trp53−/+ or trp53−/− mice displayed a greater ability to proliferate in response to EGF stimulation in vitro. The enhanced proliferative ability of trp53 deficient mice correlates with a decreased expression of the mitotic inhibitor Cdkn1a/p21cip and an increase in c-myc, a transcription factor that promotes cell cycle progression. These data show that p53 plays an essential role in limiting the potential of Müller glia to re-enter the mitotic cycle as the retina matures during postnatal development. © 2012 Wiley Periodicals, Inc.

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