Roscovitine inhibits thyroid hormone-induced tail regression of the frog tadpole and reveals a role for cyclin C/Cdk8 in the establishment of the metamorphic gene expression program.

The involvement of phosphorylation signaling pathways in postembryonic development of the frog is poorly understood. The thyroid hormone, 3, 5, 3'-triiodothyronine (T(3)), is essential for inducing tadpole metamorphosis and we show that the cyclin-dependent kinase (Cdk) inhibitor, roscovitine, prevents T(3)-dependent regression of cultured tail tips from Rana catesbeiana tadpoles. Using tail tips from precociously induced and naturally metamorphosing tadpoles, our data suggest that protein phosphorylation is important in the establishment of the T(3)-dependent proapoptotic gene expression program. Our evidence indicates that Cdk8 is the most likely candidate for this proapoptotic activity with the expression of its regulatory subunit, cyclin C, identified as a novel T(3)-responsive gene. We suggest that this activity is crucial for the genetic reprogramming required for tail regression and demonstrate that protein phosphorylation is important in T(3)-induced apoptosis in normal cells during development.