The dual function model revisited by thyroid hormone receptor knockouts: Unliganded state controlling the initiation of adult organ development while liganded state ensuring larval tissue resorption during metamorphosis.

Thyroid hormone (T3) plays a critical role in vertebrate development, particularly in postembryonic organ remodeling and maturation. Plasma level of T3 peaks during postembryonic development, which corresponds to the neonatal period in mammals when most organs/tissues mature into their adult forms or metamorphosis in amphibians when adult organs are formed de novo or remodeled from larval ones. The metamorphosis in anurans is perhaps the most dramatic, longest- and best-studied T3-regulated developmental process. Studies on metamorphosis in two highly related species, the allotetraploid Xenopus laevis and diploid Xenopus tropicalis, in over 3 decades since the cloning of T3 receptor (TR) have not only established predicted as well as novel roles of TR during development but also revealed in vivo molecular mechanisms underlying TR function. Here, we review some of these studies, with a particular focus on more recent TR knockout studies that have revealed unexpected, highly specific roles for unliganded and liganded TRs, i.e., controlling the initiation of adult organ development and ensuring larval tissue resorption, respectively.