THE XENOPUS-LAEVIS HOMOLOG TO THE NEURONAL CYCLIN-DEPENDENT KINASE (CDK5) IS EXPRESSED IN EMBRYOS BY GASTRULATION

Phosphorylation of the neuronal cytoskeletal proteins NF-H, NF-M and t au is important for normal axonal development, and is invoked in axona l injury and neurodegenerative diseases. In mammalian neurons, one kin ase that phosphorylates these axonal cytoskeletal proteins is cyclin-d ependent kinase 5 (cdk5). CdkS is a member of the family of cyclin-dep endent kinases (cdks), whose other family members regulate mitosis. Un like the other cdks, cdk5 is abundant in differentiated neurons. Embry os of the clawed frog Xenopus laevis have proved useful for studying o ther cyclin-dependent kinases, neurofilament proteins and tau during d evelopment. As a first step in studying the role of cdk5 and its effec ts on neurofilaments during Xenopus neural development, four cDNA clon es were isolated by screening a frog brain cDNA library at lowered str ingency with a cDNA probe to rat cdk5. The frog cdk5 clones encoded a protein of 292 amino acids that was 97% identical to rat cdk5. In situ hybridization demonstrated that the Xenopus cdk5 transcript, like tha t of mammals, was expressed in differentiated post-mitotic neurons. Th e high degree of sequence homology and shared neuronal expression sugg ests that the role of cdk5 in neurons is highly conserved between mamm als and amphibians. Northern blot analysis indicated that during Xenop us development, cdk5 mRNA was first expressed between the midblastula transition and gastrulation, which both occur long before neuronal dif ferentiation. These stages mark the transition from synchronous to asy nchronous cell division and are the earliest stages of zygotic gene ex pression. This early expression of Xenopus cdk5 mRNA implies a role fo r cdk5 during embryogenesis that is separate from its role as an axona l cytoskeletal protein kinase. These observations provide the foundati on for exploiting X. laevis embryos to study the role of cdk5 both in the early stages of axonal differentiation and also in early embryogen esis.