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

Abstract

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. Developmental Dynamics 237: 3787-3797, 2008.

Influence of temperature on thyroid hormone signaling and endocrine disruptor action in Rana (Lithobates) catesbeiana tadpoles

“…Such mRNA may represent vital elements associated with establishment of a commitment phase within the transcriptome under nonpermissive temperature conditions. Early work performed on the mechanistic nature of anuran metamorphosis provided evidence that aspects of initiation and execution of this developmental program could be uncoupled by inhibition of RNA transcription, controllers of the transcription complex, and protein translation or phosphorylation suggesting that a commitment point exists early on where subsequent reversal of the TH-mediated process cannot occur and all effectors required for completion of metamorphosis are established (Buckbinder and Brown, 1992;Ji et al, 2007;Kanamori and Brown, 1993;Skirrow et al, 2008). It presently remains unclear whether such molecular mechanisms are involved in temperature-dependent regulation of metamorphosis.…”

C‐fin: A cultured frog tadpole tail fin biopsy approach for detection of thyroid hormone‐disrupting chemicals

“…The C‐fin assay is responsive to TH agonists and antagonists, as indicated by exposure profiles upon administration of Triac and roscovitine (Fig. 4), 11, 20, 25 each with different, yet possibly overlapping, mechanisms 10, 11.…”

Apoptosis in amphibian organs during metamorphosis

“…In contrast, inhibition of protein kinase C prevents TH-induced tail regression [110]. In addition, the activity of Cdk8 together with its regulatory unit, cyclin C, whose expression is TH dependent, is required for the tail shortening, suggesting their proapoptotic role [111]. …”