Oligodendrocyte precursor differentiation is perturbed in the absence of the cyclin-dependent kinase inhibitor p27(Kip1)

被引:224
|
作者
CasacciaBonnefil, P
Tikoo, R
Kiyokawa, H
Friedrich, V
Chao, MV
Koff, A
机构
[1] MEM SLOAN KETTERING CANC CTR,PROGRAM MOL BIOL,NEW YORK,NY 10021
[2] CORNELL UNIV,COLL MED,DEPT ANAT & CELL BIOL,NEW YORK,NY 10021
[3] CORNELL UNIV,COLL MED,DEPT NEUROL & NEUROSCI,NEW YORK,NY 10021
[4] CUNY MT SINAI SCH MED,BROOKDALE CTR MOL BIOL,NEW YORK,NY 10029
关键词
oligodendrocyte progenitor cells; cell proliferation; differentiation; CKI p27(Kip1);
D O I
10.1101/gad.11.18.2335
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 p27(Kip1), 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 G(1)/G(0) 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.
引用
收藏
页码:2335 / 2346
页数:12
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