Thyroid hormone receptor beta is critical for intestinal remodeling during Xenopus tropicalis metamorphosis

Background Thyroid hormone (T3) is critical for development in all vertebrates. The mechanism underlying T3 effect has been difficult to study due to the uterus-enclosed nature of mammalian embryos. Anuran metamorphosis, which is dependent on T3 but independent of maternal influence, is an excellent model to study the roles of T3 and its receptors (TRs) during vertebrate development. We and others have reported various effects of TR knockout (TR alpha and TR beta) during Xenopus tropicalis development. However, these studies were largely focused on external morphology. Results We have generated TR beta knockout animals containing an out-frame-mutation of 5 base deletion by using the CRISPR/Cas9 system and observed that TR beta knockout does not affect premetamorphic tadpole development. We have found that the basal expression of direct T3-inducible genes is increased but their upregulation by T3 is reduced in the intestine of premetamorphic homozygous TR beta knockout animals, accompanied by reduced target binding by TR. More importantly, we have observed reduced adult stem cell proliferation and larval epithelial apoptosis in the intestine during T3-induced metamorphosis. Conclusions Our data suggest that TR beta plays a critical role in intestinal remodeling during metamorphosis.