PT - JOURNAL ARTICLE AU - Michael A. Dyer AU - Constance L. Cepko TI - p27<sup>Kip1</sup> and p57<sup>Kip2</sup> Regulate Proliferation in Distinct Retinal Progenitor Cell Populations AID - 10.1523/JNEUROSCI.21-12-04259.2001 DP - 2001 Jun 15 TA - The Journal of Neuroscience PG - 4259--4271 VI - 21 IP - 12 4099 - http://www.jneurosci.org/content/21/12/4259.short 4100 - http://www.jneurosci.org/content/21/12/4259.full SO - J. Neurosci.2001 Jun 15; 21 AB - In the developing vertebrate retina, progenitor cell proliferation must be precisely regulated to ensure appropriate formation of the mature tissue. Cyclin kinase inhibitors have been implicated as important regulators of proliferation during development by blocking the activity of cyclin–cyclin-dependent kinase complexes. We have found that the p27Kip1 cyclin kinase inhibitor regulates progenitor cell proliferation throughout retinal histogenesis. p27Kip1 is upregulated during the late G2/early G1 phase of the cell cycle in retinal progenitor cells, where it interacts with the major retinal D-type cyclin–cyclin D1. Mice deficient for p27Kip1exhibited an increase in the proportion of mitotic cells throughout development as well as extensive apoptosis, particularly during the later stages of retinal histogenesis. Retroviral-mediated overexpression of p27Kip1 in mitotic retinal progenitor cells led to premature cell cycle exit yet had no dramatic effects on Müller glial or bipolar cell fate specification as seen with the Xenopus cyclin kinase inhibitor, p27Xic1. Consistent with the overexpression of p27Kip1, mice lacking one or both alleles of p27Kip1 maintained the same relative ratios of each major retinal cell type as their wild-type littermates. During the embryonic stages of development, when both p27Kip1and p57Kip2 are expressed in retinal progenitor cells, they were found in distinct populations, demonstrating directly that different retinal progenitor cells are heterogeneous with respect to their expression of cell cycle regulators.