Millipore Home

• Home
• Products
• Services
• Learning Center
• Tech Library
• Support
• Company

Product Reference

Cyclin-dependent kinase-2 controls oligodendrocyte progenitor cell cycle progression and is downregulated in adult oligodendrocyte progenitors.

Author	Shibeshih Belachew, Adan A Aguirre, Hang Wang, François Vautier, Xiaoqing Yuan, Stacie Anderson, Martha Kirby, Vittorio Gallo
Citation Information	The Journal of neuroscience : the official journal of the Society for Neuroscience, 22:8553-62 (2002)
Keywords	Animals, CDC2-CDC28 Kinases, Cell Cycle, Cell Differentiation, Cell Line, Cell Lineage, Cells, Cultured, Cyclin-Dependent Kinase 2, Cyclin-Dependent Kinases, Down-Regulation, Enzyme Activation, Gene Expression Regulation, Developmental, Green Fluorescent Proteins, Luminescent Proteins, Mice, Mice, Transgenic, Mitosis, Oligodendroglia, Protein-Serine-Threonine Kinases, Rats, Rats, Sprague-Dawley, Stem Cells, Transfection
Related Products	05-347
Pub Med ID	12351729

Proliferation of oligodendrocyte progenitor (OP) cells is a crucial process controlling myelination in the CNS. Previous studies demonstrated a correlation between OP proliferation rate and cyclin E/cyclin-dependent kinase-2 (cdk2) activity. To establish a causal link between cyclin E/cdk2 activity and OP proliferation, we selectively modulated cdk2 activity in vitro by transfection of cultured OP cells. Dominant-negative (Dn)-cdk2 overexpression inhibited mitogen-induced OP cell proliferation, whereas wild-type (wt)-cdk2 prevented cell cycle arrest caused by anti-mitotic signals. Dn-cdk2- or wt-cdk2-mediated regulation of G(1)/S transition, per se, did not influence initiation of OP differentiation. To study the function of cyclin E/cdk2 in OP cells during development in vivo, we analyzed cdk2 and cyclin E expression in cells acutely isolated from transgenic mice expressing the green fluorescent protein (GFP) under the control of the 2'-3'-cyclic nucleotide 3'-phosphodiesterase gene promoter. Both cyclin E/cdk2 protein levels and activity were decreased in GFP(+) oligodendrocyte lineage cells between postnatal days 4 and 30. Immunostaining of NG2(+)/GFP(+) OP cells in brain tissue sections showed a 90% decrease in overall cell proliferation and cdk2 expression between perinatal and adult cells. However, cdk2 expression within the proliferating (i.e., expressing the proliferating cell nuclear antigen) OP cell population was maintained throughout development. Our data indicate that: (1) cyclin E/cdk2 activity plays a pivotal function in OP cell cycle decisions occurring at G(1)/S checkpoint; (2) initiation of OP differentiation is independent of cyclinE/cdk2 checkpoint, and (3) intrinsic differences in cyclin E/cdk2 expression and activity may underlie the slowly proliferative state that characterizes so-called quiescent adult OP cells in vivo.