Molecular features of thyroid hormone-regulated skin remodeling in Xenopus laevis during metamorphosis.

Amphibian body skin provides an opportunity to investigate the molecular mechanism of thyroid hormone (TH)-dependent organ remodeling during metamorphosis. Global gene expression changes in the TH-dependent body skin remodeling were studied with microarray analysis. We identified 401 genes that were differentially expressed more than fourfold for 7 days after TH-treatment. As expected, larval- and adult-type keratin genes were significantly inactivated and activated, respectively. The expression changes of the Gene Ontology annotated genes demonstrated significant correlation with the morphological and physiological changes in body skin metamorphosis. The 'transcription and proteolysis' category genes were first upregulated 1 day after TH-treatment. Subsequently, the 'cell cycle' category genes were activated at 3 days. The 'defense response' and 'immune response' category genes were the late TH-response genes, which were downregulated and upregulated at 5 and 7 days, respectively. From these genes, adult-type keratin-c (xak-c) gene was selected as a suitable gene to visually monitor the emergence of adult-type epidermal cells during skin remodeling, because the gene is specifically expressed in adult epidermal basal cells. We generated enhanced green fluorescent protein (EGFP)-transgenic Xenopus laevis driven by the promoter of xak-c gene. The keratin promoter faithfully expressed the EGFP gene in adult-type basal cells. Spatial and temporal EGFP-fluorescence patterns of filial 1 (F1)-offspring tadpoles visually demonstrated an event of sequential replacement of larval keratinocytes with the newly generated adult counterparts.