Abstract
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 p27Kip1cyclin kinase inhibitor regulates progenitor cell proliferation throughout retinal histogenesis. p27Kip1is upregulated during the late G2/early G1phase 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 p27Kip1in 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 theXenopuscyclin kinase inhibitor, p27Xic1. Consistent with the overexpression of p27Kip1, mice lacking one or both alleles of p27Kip1maintained the same relative ratios of each major retinal cell type as their wild-type littermates. During the embryonic stages of development, when both p27Kip1and p57Kip2are 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.
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Dates
Type | When |
---|---|
Created | 7 years, 4 months ago (April 4, 2018, 10:15 p.m.) |
Deposited | 2 years, 4 months ago (April 13, 2023, 10 a.m.) |
Indexed | 4 weeks, 2 days ago (Aug. 3, 2025, 12:12 a.m.) |
Issued | 24 years, 2 months ago (June 15, 2001) |
Published | 24 years, 2 months ago (June 15, 2001) |
Published Online | 24 years, 2 months ago (June 15, 2001) |
Published Print | 24 years, 2 months ago (June 15, 2001) |
@article{Dyer_2001, title={p27Kip1and p57Kip2Regulate Proliferation in Distinct Retinal Progenitor Cell Populations}, volume={21}, ISSN={1529-2401}, url={http://dx.doi.org/10.1523/jneurosci.21-12-04259.2001}, DOI={10.1523/jneurosci.21-12-04259.2001}, number={12}, journal={The Journal of Neuroscience}, publisher={Society for Neuroscience}, author={Dyer, Michael A. and Cepko, Constance L.}, year={2001}, month=jun, pages={4259–4271} }