Liver development during Xenopus tropicalis metamorphosis is controlled by T3-activation of WNT signaling

Thyroid hormone (T3) regulates vertebrate organ development, growth, and metabolism through the T3 receptor (TR). Due to maternal influence in mammals, it has been difficult to study if and how T3 regulates liver development. Liver remodeling during anuran metamorphosis resembles liver maturation in mammals and is controlled by T3. We generated Xenopus tropicalis animals with both TRα and TRβ genes knocked out and found that TR double knockout liver had developmental defects such as reduced cell proliferation and failure to undergo hepatocyte hypertrophy or activate urea cycle gene expression. RNA-seq analysis showed that T3 activated canonical Wnt pathway in the liver. Particularly, Wnt11 was activated in both fibroblasts and hepatic cells, and in turn, likely promoted the proliferation and maturation of hepatocytes. Our study offers new insights into not only how T3 regulates liver development but also on potential means to improve liver regeneration.