ACTIVITY AND EXPRESSION PATTERN OF CYCLIN-DEPENDENT KINASE-5 IN THE EMBRYONIC MOUSE NERVOUS-SYSTEM

Cyclin-dependent kinase 5 (cdk5) was originally isolated on the basis of its close primary sequence homology to the human cdc2 serine/threon ine kinase, the prototype of the cyclin-dependent kinases. While kinas e activities of both cdc2 and cdk2 are detected in proliferating cells and are essential for cells to progress through the key transition po ints of the cell cycle, cdk5 kinase activity has been observed only in lysates of adult brain. In this study, we compared the activity and e xpression of cdk5 with that of cdc2 and cdk2 in the embryonic mouse fo rebrain. The expression and activity of cdk5 increased progressively a s increasing numbers of cells exited the proliferative cycle. In contr ast, the expression and activity of cdc2 and cdk2 were maximum at gest ational day 11 (Ell) when the majority of cells were proliferating and fell to barely detectable levels at E17 at the end of the cytogenetic period. Immunohistochemical studies showed that cdk5 is expressed in postmitotic neurons but not in glial cells or mitotically active cells . Expression of cdk5 was concentrated in fasciculated axons of postmit otic neurons. In contrast to other cell division cycle kinases to whic h it is closely related, cdk5 appears not to be expressed in dividing cells in the developing brain. These observations suggest that cdk5 ma y have a role in neuronal differentiation but not in the cell division cycle in the embryonic nervous system.