Expression Profiles of Novel Thyroid Hormone-Responsive Genes and Proteins in the Tail ofXenopus laevisTadpoles Undergoing Precocious Metamorphosis

Abstract

Thyroid hormones (THs) are critical for the growth, development, and homeostasis of many organisms and are necessary for metamorphosis of Xenopus laevis tadpoles. TH-induced metamorphosis requires alterations in the transcriptome and the proteome. However, only a few of the molecular components of this developmental program have been identified and their interrelationship remains unclear. Using a cDNA array comprised of 420 known anuran genes and quantitative PCR, we have identified 93 TH-responsive genes in the tail of premetamorphic tadpoles after exogenous administration of T3. Fifty-three of these mRNA transcripts have not previously been characterized as TH responsive in any species. The gene expression profiles show distinctive temporal patterns with most transcript steady-state levels increasing after induction of metamorphosis. Two-dimensional gel electrophoresis of total protein extracts from the tail shows changes in steady-state levels of many proteins after T3 treatment. Of the up-regulated proteins, 10 were identified by peptide mass mapping. These data identify potential components involved in the regulation of Xenopus tail regression by T3 and begin to address a critical question regarding the interrelationship between the transcriptome and the proteome in TH-dependent developmental processes.

Coordination of mitochondrial biogenesis by thyroid hormone

“…Yet, similar results have been observed in other tissues in vivo (such as skeletal muscle) and in cell culture experiments (Clement et al, 2002;Helbing et al, 2003;Miller et al, 2001;Shih et al, 2004), thereby emphasising the importance of TH in systemic physiology. Differentially regulated genes are involved in a wide variety of cellular functions including translation, protein turnover, apoptosis, and metabolism.…”

“…Serum TH levels are detectable shortly after the formation of the functional gland and consequently trigger metamorphosis. Microarrays and subtractive hybridisation approaches confirmed early and late gene induction (Denver et al, 1997;Helbing et al, 2003). In pituitary GC cells and HepG2 cells (stably expressing functionally active TRs), both patterns have also been observed (Miller et al, 2001;Shih et al, 2004).…”

“…These expression patterns have not only been found in liver but also in whole organisms (e.g. Xenopus laevis), different rodent tissues, and different cell models (Helbing et al, 2003;Quignodon et al, 2007;Chattopadhyay et al, 2007;Miller et al, 2001;Shih et al, 2004).…”

T3-mediated gene expression is independent of PGC-1α

“…Whereas ~ 50% of T3-regulated genes were rapidly induced within 6 hours after the administration of T3 in vivo, another ~ 50% of T3 target genes were differentially regulated after a gap period of 12-24 hours within 48 hours (Weitzel et al, 2001b;Weitzel et al, 2003a). Interestingly, similar expression patterns have been observed 300 in the tail of Xenopus laevis tadpoles and several cell systems (Helbing et al, 2003;Moeller et al, 2005;Shih et al, 2004). This observation leads to the assumption that the delayed expressed genes may be indirectly regulated via an intermediate factor.…”

Genistein prevents thyroid hormone‐dependent tail regression of Rana catesbeiana tadpoles by targetting protein kinase C and thyroid hormone receptor α

“…Tadpole tail resorption, one of the last changes during metamorphosis, is mediated by apoptotic pathways and is entirely controlled by TH. This process can be precociously induced by exogenous administration of T 3 (Wang and Brown, 1993;Brown et al, 1996;Helbing et al, 2003) matching the onset and completion of natural metamorphosis (Wang and Brown, 1993;Helbing et al, 2003). TH action at the cellular level is highly conserved from frogs to humans and is primarily mediated by mechanisms involving TH binding to specific nuclear thyroid hormone receptors (TRs) that regulate gene expression (Shi, 2000;Yen, 2001).…”