Thyroid hormone (T3) have broad and diverse effects in vertebrates. It affects metabolisms in different organs and regulates development. In mammals, the T3 level in the plasma peaks around birth when many organs/tissues develop/mature into their adult forms (Tata, 1993). This postembryonic period bears strong similarities to amphibian metamorphosis, which has served as a model for studying the roles of T3 in diverse developmental processes in vertebrates, from de novo adult tissue development, removal and remodeling of larval tissues, to organ regeneration (Gilbert & Frieden, 1981; Gilbert, Tata, & Atkinson, 1996; Li, Zhang, & Amaya, 2016; Marshall et al., 2019; Shi, 1999, Shi, 2013; Tata, 1993; Wang & Shi, 2021; Yakushiji, Yokoyama, & Tamura, 2009). Amphibian metamorphosis involves drastic changes in many organs/tissues. In anurans, such as Xenopus tropicalis and Xenopus laevis, essentially every organ/tissue is changed during metamorphosis. Some, such as the tail and gills, are larval specific and are resorbed completely by the end of metamorphosis, while others, such as the limbs, function in the adult frogs only and form de novo during metamorphosis (Nieuwkoop & Faber, 1965; Shi, 1999; Tata, 1993). The rest of the organs, which are present in both tadpoles and frogs, are also remodeled extensively in order to adapt to their roles in the frogs. Such broad, diverse changes and their dependence on T3 have made anuran metamorphosis a unique and highly advantageous model to study how T3 regulates different tissue transformations during vertebrate development (Shi, 1999; Tata, 1993).

In this chapter, we will review some of the molecular and genetic studies on the mechanisms of T3 regulation of metamorphosis in the two highly related species, Xenopus tropicalis and Xenopus laevis. The pseudo-tetraploid Xenopus laevis has been used for molecular and transgenic studies since the late 1980s, shortly after the cloning of the thyroid hormone receptors (TRs) (Buchholz, Paul, Fu, & Shi, 2006; Shi, 1999; Tata, 1993). More recently, with the development of gene editing technologies, Xenopus tropicalis has become the model of choice for gene knockout studies due to its diploid nature. Such analyses in Xenopus tropicalis and Xenopus laevis have not only revealed the functions of TRs and underlying mechanisms during amphibian metamorphosis but also provided evidence for the conservation in T3 signaling in vertebrate development.