TEMPORAL AND SPATIAL PATTERNS OF EXPRESSION OF P35, A REGULATORY SUBUNIT OF CYCLIN-DEPENDENT KINASE-5, IN THE NERVOUS-SYSTEM OF THE MOUSE

The protein p35 is a regulatory subunit of cyclin-dependent kinase 5. It has no recognized homology to cyclins but binds to and activates cy clin-dependent kinase 5 directly in the absence of other protein molec ules. Cyclin-dependent kinase 5 was initially isolated by homology to the key cell cycle regulator cdc2 kinase and later identified as a neu ronal kinase that phosphorylates histone H1, tau or neurofilaments. Th is kinase is localized in axons of the developing and mature nervous s ystem. To understand the role of p35 as a regulator of cyclin-dependen t kinase 5 activity in the CNS, we examined the pattern of expression of p35 mRNA in the nervous system of embryonic, early postnatal and ad ult mice. In separate experiments, we also examined the spatial distri bution of cyclin-dependent kinase 5 mRNA and the activity of cyclin-de pendent kinase 5/p35 kinase complex. Postmitotic cells express p35 mRN A immediately after they leave the zones of cell proliferation. It is also expressed in developing axonal tracts in the brain. Cyclin-depend ent kinase 5 mRNA is present in postmitotic and in proliferative cells throughout the embryonic central nervous system. During early postnat al period signal for p35 mRNA declines while that for cyclin-dependent kinase 5 mRNA increases throughout the brain. In the adult brain alth ough both p35 and cyclin-dependent kinase 5 mRNAs are expressed at rel atively high levels in certain structures associated with the limbic s ystem, considerable differences exist in the patterns of their distrib ution in other parts of the brain. These data suggest that the p35/cyc lin-dependent kinase 5 complex may be associated with early events of neuronal development such as neuronal migration and axonal growth whil e in the limbic system of the mature brain it may be associated with t he maintenance of neuronal plasticity.