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 (TRα and TRβ) during Xenopus tropicalis development. However, these studies were largely focused on external morphology. We have generated TRβ knockout animals containing an out-frame-mutation of 5 base deletion by using the CRISPR/Cas9 system and observed that TRβ 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 TRβ 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. Our data suggest that TRβ plays a critical role in intestinal remodeling during metamorphosis.

中文翻译：

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甲状腺激素受体β对热带非洲爪蟾变态过程中的肠道重塑至关重要

甲状腺激素 (T3) 对所有脊椎动物的发育都至关重要。由于哺乳动物胚胎的子宫封闭性质，很难研究 T3 效应的潜在机制。Anuran 变态依赖于 T3 但独立于母体影响，是研究 T3 及其受体 (TRs) 在脊椎动物发育过程中作用的极好模型。我们和其他人已经报道了在热带爪蟾发育过程中 TR 敲除（TRα 和 TRβ）的各种影响。然而，这些研究主要集中在外部形态上。我们使用 CRISPR/Cas9 系统生成了包含 5 个碱基缺失的外框突变的 TRβ 敲除动物，并观察到 ​​TRβ 敲除不影响变质前蝌蚪的发育。我们发现直接 T3 诱导基因的基础表达增加，但 T3 的上调在前变质纯合 TRβ 敲除动物的肠道中减少，伴随着 TR 的靶结合减少。更重要的是，我们观察到 T3 诱导的变态过程中成体干细胞增殖和幼虫上皮细胞凋亡减少。我们的数据表明，TRβ 在变态过程中的肠道重塑中起关键作用。