Oligodendrocyte precursor differentiation is perturbed in the absence of the cyclin-dependent kinase inhibitor p27Kip1
- Patrizia Casaccia-Bonnefil1,
- Ravi Tikoo2,
- Hiroaki Kiyokawa3,
- Victor Friedrich, Jr.4,
- Moses V. Chao1, and
- Andrew Koff3,5
- 1Department of Cell Biology and Anatomy, and 2Department of Neurology and Neuroscience, Cornell University Medical College, New York, New York 10021; 3Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021; 4Brookdale Center for Molecular Biology, Mt. Sinai School of Medicine, New York, New York 10029
Abstract
During development of the central nervous system, oligodendrocyte progenitor cells (O-2A) undergo an orderly pattern of cell proliferation and differentiation, culminating in the ability of oligodendrocytes to myelinate axons. Here we report that p27Kip1, a cyclin-dependent kinase inhibitor, is an important component of the decision of O-2A cells to withdraw from the cell cycle. In vitro, accumulation of p27 correlates with differentiation of oligodendrocytes. Furthermore, only a fraction of O-2A cells derived from p27-knockout mice differentiate successfully compared to controls. Inability to differentiate correlates with continued proliferation, suggesting that p27 is an important component of the machinery required for the G1/G0 transition in O-2A cells. In vivo, expansion of O-2A precursors before withdrawal, in part, leads to a greater number of oligodendrocytes. Together these data indicate a role for p27 during the decision to withdraw from the cell cycle in the oligodendrocyte lineage.
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Footnotes
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↵5 Corresponding author.
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E-MAIL a-koff{at}ski.mskcc.org; FAX (212) 639-2861.
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- Received April 18, 1997.
- Accepted July 21, 1997.
- Cold Spring Harbor Laboratory Press