Unbound MEDLINE

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

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/p21(cip) 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.

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  • Publisher Full Text

    • Authors

    Ueki Y, Karl MO, Sudar S, Pollak J, Taylor RJ, Loeffler K, Wilken MS, Reardon S, Reh TA

    Institution

    Department of Biological Structure, University of Washington, Seattle, Washington, USA.

    Source

    Glia 60:10 2012 Oct pg 1579-89

    MeSH

    Activating Transcription Factor 3
    Age Factors
    Animals
    Animals, Newborn
    Basic Helix-Loop-Helix Transcription Factors
    Cell Proliferation
    Cells, Cultured
    Cyclin-Dependent Kinase Inhibitor p21
    Epidermal Growth Factor
    Gene Expression Regulation, Developmental
    Glial Fibrillary Acidic Protein
    Green Fluorescent Proteins
    Immediate-Early Proteins
    Inhibitor of Differentiation Protein 1
    Mice
    Mice, Inbred C57BL
    Mice, Transgenic
    Neuroglia
    Organ Culture Techniques
    RNA, Messenger
    Repressor Proteins
    Retina
    Time Factors
    Tumor Suppressor Protein p53
    Tumor Suppressor Proteins

    Pub Type(s)

    In Vitro
    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.

    Language

    eng

    PubMed ID

    22777914