P53 is required for the developmental restriction in Müller glial proliferation in mouse retina
Article first published online: 6 JUL 2012
Copyright © 2012 Wiley Periodicals, Inc.
Volume 60, Issue 10, pages 1579–1589, October 2012
How to Cite
Ueki, Y., Karl, M. O., Sudar, S., Pollak, J., Taylor, R. J., Loeffler, K., Wilken, M. S., Reardon, S. and Reh, T. A. (2012), P53 is required for the developmental restriction in Müller glial proliferation in mouse retina. Glia, 60: 1579–1589. doi: 10.1002/glia.22377
- Issue published online: 16 AUG 2012
- Article first published online: 6 JUL 2012
- Manuscript Accepted: 5 JUN 2012
- Manuscript Received: 8 APR 2012
- Vision Core Grant. Grant Numbers: P30EY01730, 1R01EY021482
- Developmental Biology Predoctoral Training Grant, NICHHD. Grant Number: T32HD007183
- NSF Graduate Research Fellowship. Grant Number: DGE-0718124
- Deutsche Forschungsgemeinschaft (CRTD core and seed grant) and a ProRetina Germany PhD fellowship
- cell cycle;
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.