Oligodendrocyte precursor differentiation is perturbed in the absence of the cyclin-dependent kinase inhibitor p27Kip1

  1. Patrizia Casaccia-Bonnefil1,
  2. Ravi Tikoo2,
  3. Hiroaki Kiyokawa3,
  4. Victor Friedrich, Jr.4,
  5. Moses V. Chao1, and
  6. Andrew Koff3,5
  1. 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.

Keywords

Footnotes

  • 5 Corresponding author.

  • E-MAIL a-koff{at}ski.mskcc.org; FAX (212) 639-2861.

    • Received April 18, 1997.
    • Accepted July 21, 1997.
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