P53 is required for the developmental restriction in Müller glial proliferation in mouse retina.
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.
Department of Biological Structure, University of Washington, Seattle, Washington, USA.
SourceGlia 60:10 2012 Oct pg 1579-89
MeSHActivating Transcription Factor 3
Basic Helix-Loop-Helix Transcription Factors
Cyclin-Dependent Kinase Inhibitor p21
Epidermal Growth Factor
Gene Expression Regulation, Developmental
Glial Fibrillary Acidic Protein
Green Fluorescent Proteins
Inhibitor of Differentiation Protein 1
Mice, Inbred C57BL
Organ Culture Techniques
Tumor Suppressor Protein p53
Tumor Suppressor Proteins
Pub Type(s)In Vitro
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.