{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T05:18:03Z","timestamp":1790486283298,"version":"4.1.0"},"reference-count":77,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Thyroid\u00ae"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\n                      There are two highly conserved thyroid hormone (triiodothyronine [T3]) receptor (\n                      <jats:italic toggle=\"yes\">TR<\/jats:italic>\n                      ) genes,\n                      <jats:italic toggle=\"yes\">TR\u03b1<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">TR\u03b2<\/jats:italic>\n                      , in all vertebrates, and the expression of\n                      <jats:italic toggle=\"yes\">TR\u03b1<\/jats:italic>\n                      but not\n                      <jats:italic toggle=\"yes\">TR\u03b2<\/jats:italic>\n                      is activated earlier than T3 synthesis during development. In human, high levels of T3 are present during the several months around birth, and T3 deficiency during this period causes severe developmental abnormalities including skeletal and intestinal defects. It is, however, difficult to study this period in mammals as the embryos and neonates depend on maternal supply of nutrients for survival. However,\n                      <jats:italic toggle=\"yes\">Xenopus tropicalis<\/jats:italic>\n                      undergoes a T3-dependent metamorphosis, which drastically changes essentially every organ in a tadpole. Of interest is intestinal remodeling, which involves near complete degeneration of the larval epithelium through apoptosis. Concurrently, adult intestinal stem cells are formed\n                      <jats:italic toggle=\"yes\">de novo<\/jats:italic>\n                      and subsequently give rise to the self-renewing adult epithelial system, resembling intestinal maturation around birth in mammals. We have previously demonstrated that T3 signaling is essential for the formation of adult intestinal stem cells during metamorphosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We studied the function of endogenous TR\u03b1 in the tadpole intestine by using knockout animals and RNA-seq analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      We observed that removing endogenous TR\u03b1 caused defects in intestinal remodeling, including drastically reduced larval epithelial cell death and adult intestinal stem cell proliferation. Using RNA-seq on intestinal RNA from premetamorphic wild-type and\n                      <jats:italic toggle=\"yes\">TR\u03b1<\/jats:italic>\n                      -knockout tadpoles treated with or without T3 for one day, before any detectable T3-induced cell death and stem cell formation in the tadpole intestine, we identified more than 1500 genes, which were regulated by T3 treatment of the wild-type but not\n                      <jats:italic toggle=\"yes\">TR\u03b1<\/jats:italic>\n                      -knockout tadpoles. Gene Ontology and biological pathway analyses revealed that surprisingly, these TR\u03b1-regulated genes were highly enriched with cell cycle-related genes, in addition to genes related to stem cells and apoptosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Our findings suggest that TR\u03b1-mediated T3 activation of the cell cycle program is involved in larval epithelial cell death and adult epithelial stem cell development during intestinal remodeling.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/thy.2020.0022","type":"journal-article","created":{"date-parts":[[2020,6,9]],"date-time":"2020-06-09T07:21:52Z","timestamp":1591687312000},"page":"128-142","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":33,"title":["Analysis of Thyroid Hormone Receptor \u03b1-Knockout Tadpoles Reveals That the Activation of Cell Cycle Program Is Involved in Thyroid Hormone-Induced Larval Epithelial Cell Death and Adult Intestinal Stem Cell Development During\n                    <i>Xenopus tropicalis<\/i>\n                    Metamorphosis"],"prefix":"10.1177","volume":"31","author":[{"given":"Yuta","family":"Tanizaki","sequence":"first","affiliation":[{"name":"Section on Molecular Morphogenesis, Cell Regulation and Development Affinity Group, Division of Molecular and Cellular Biology, and Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Shibata","sequence":"additional","affiliation":[{"name":"Section on Molecular Morphogenesis, Cell Regulation and Development Affinity Group, Division of Molecular and Cellular Biology, and Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Bioinformatics and Scientific Programming Core, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Bo","family":"Shi","sequence":"additional","affiliation":[{"name":"Section on Molecular Morphogenesis, Cell Regulation and Development Affinity Group, Division of Molecular and Cellular Biology, and Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2021,1,12]]},"reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2010.12.020"},{"key":"e_1_3_6_3_2","first-page":"94","article-title":"The role of thyroid hormones in prenatal and neonatal neurological development\u2014current perspectives","volume":"14","author":"Porterfield SP","year":"1993","unstructured":"Porterfield SP, , Hendrich CE. 1993. 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