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1 Department of Cell Biology and Anatomy, and
2 Department of Neurology and Neuroscience, Cornell University
Medical College, New York, New York 10021;
3 Molecular Biology
Program, Memorial Sloan-Kettering Cancer Center, New York, New York
10021;
4 Brookdale Center for Molecular Biology, Mt. Sinai
School of Medicine, New York, New York 10029
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.
[Key Words: Oligodendrocyte progenitor cells; cell proliferation; differentiation; CKI p27Kip1]
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