CHANGES IN THE ACTIVITY OF CDK2 AND CDK5 ACCOMPANY DIFFERENTIATION OFRAT PRIMARY OLIGODENDROCYTES

Oligodendrocytes, the myelinating cells of the central nervous system, are terminally differentiated cells that originate through asynchrono us waves of proliferation and differentiation of precursors present at birth. Withdrawal from cell cycle and onset of differentiation are ti ghtly linked and depend on an intrinsic program modulated by the actio n of growth factors. p27 plays a central and obligatory role in the in itiation of oligodendrocyte differentiation and cessation of prolifera tion. In this paper, we have characterized the role of modulation of c dk2 and cdk5 kinase activity during the process of oligodendrocyte pre cursor differentiation. As rat primary oligodendrocytes differentiate in culture there is a fail in cdk2 activity and a rise in cdk5 activit y as well as an increase in the cdk inhibitor, p27 protein. The declin e in cdk2 activity is not accompanied by a drop in cdk2 protein level, suggesting that it results from inhibition of cdk2 activation rather than decreased protein expression. Taken together, these data suggest that oligodendrocytes may withdraw from the cell cycle at G1-S transit ion through inactivation of cdk2 activity, possibly initiated by incre asing amount of p27, and that cdk5 may have a role until now unrecogni zed in the differentiation of oligodendrocytes. (C) 1998 Wiley-Liss, I nc.