XB-ART-49956
Endocrinology
2015 Feb 01;1562:721-34. doi: 10.1210/en.2014-1439.
Show Gene links
Show Anatomy links
Unliganded thyroid hormone receptor α controls developmental timing in Xenopus tropicalis.
Wen L
,
Shi YB
.
???displayArticle.abstract???
Thyroid hormone (T3) affects adult metabolism and postembryonic development in vertebrates. T3 functions mainly via binding to its receptors (TRs) to regulate gene expression. There are 2 TR genes, TRα and TRβ, with TRα more ubiquitously expressed. During development, TRα expression appears earlier than T3 synthesis and secretion into the plasma. This and the ability of TRs to regulate gene expression both in the presence and absence of T3 have indicated a role for unliganded TR during vertebrate development. On the other hand, it has been difficult to study the role of unliganded TR during development in mammals because of the difficulty to manipulate the uterus-enclosed, late-stage embryos. Here we use amphibian development as a model to address this question. We have designed transcriptional activator-like effector nucleases (TALENs) to mutate the TRα gene in Xenopus tropicalis. We show that knockdown of TRα enhances tadpole growth in premetamorphic tadpoles, in part because of increased growth hormone gene expression. More importantly, the knockdown also accelerates animal development, with the knockdown animals initiating metamorphosis at a younger age and with a smaller body size. On the other hand, such tadpoles are resistant to exogenous T3 treatment and have delayed natural metamorphosis. Thus, our studies not only have directly demonstrated a critical role of endogenous TRα in mediating the metamorphic effect of T3 but also revealed novel functions of unliganded TRα during postembryonic development, that is, regulating both tadpole growth rate and the timing of metamorphosis.
???displayArticle.pubmedLink??? 25456066
???displayArticle.pmcLink??? PMC4298314
???displayArticle.link??? Endocrinology
???displayArticle.grants??? [+]
Intramural NIH HHS
References [+] :
Amaya, Frog genetics: Xenopus tropicalis jumps into the future. 1998, Pubmed , Xenbase
Astapova, The nuclear corepressor, NCoR, regulates thyroid hormone action in vivo. 2008, Pubmed
Bilesimo, Specific histone lysine 4 methylation patterns define TR-binding capacity and differentiate direct T3 responses. 2011, Pubmed , Xenbase
Brown, Amphibian metamorphosis. 2007, Pubmed , Xenbase
Brucker-Davis, Prevalence and mechanisms of hearing loss in patients with resistance to thyroid hormone. 1996, Pubmed
Buchholz, A dominant-negative thyroid hormone receptor blocks amphibian metamorphosis by retaining corepressors at target genes. 2003, Pubmed , Xenbase
Buchholz, Transgenic analysis reveals that thyroid hormone receptor is sufficient to mediate the thyroid hormone signal in frog metamorphosis. 2004, Pubmed , Xenbase
Buchholz, Molecular and developmental analyses of thyroid hormone receptor function in Xenopus laevis, the African clawed frog. 2006, Pubmed , Xenbase
Buchholz, Gene-specific changes in promoter occupancy by thyroid hormone receptor during frog metamorphosis. Implications for developmental gene regulation. 2005, Pubmed , Xenbase
Buchholz, Spatial and temporal expression pattern of a novel gene in the frog Xenopus laevis: correlations with adult intestinal epithelial differentiation during metamorphosis. 2004, Pubmed , Xenbase
Burke, Co-repressors 2000. 2000, Pubmed
Cermak, Efficient design and assembly of custom TALEN and other TAL effector-based constructs for DNA targeting. 2011, Pubmed
Das, Multiple thyroid hormone-induced muscle growth and death programs during metamorphosis in Xenopus laevis. 2002, Pubmed , Xenbase
Denver, Neuroendocrinology of amphibian metamorphosis. 2013, Pubmed
Denver, Thyroid hormone receptor subtype specificity for hormone-dependent neurogenesis in Xenopus laevis. 2009, Pubmed , Xenbase
Eliceiri, Quantitation of endogenous thyroid hormone receptors alpha and beta during embryogenesis and metamorphosis in Xenopus laevis. 1994, Pubmed , Xenbase
Evans, The steroid and thyroid hormone receptor superfamily. 1988, Pubmed
Flamant, Congenital hypothyroid Pax8(-/-) mutant mice can be rescued by inactivating the TRalpha gene. 2002, Pubmed
Flamant, Thyroid hormone receptors: lessons from knockout and knock-in mutant mice. 2003, Pubmed
Forrest, Thyroid hormone receptor beta is essential for development of auditory function. 1996, Pubmed
Fu, Novel double promoter approach for identification of transgenic animals: A tool for in vivo analysis of gene function and development of gene-based therapies. 2002, Pubmed , Xenbase
Furlow, The transcription factor basic transcription element-binding protein 1 is a direct thyroid hormone response gene in the frog Xenopus laevis. 2002, Pubmed , Xenbase
Furlow, In vitro and in vivo analysis of the regulation of a transcription factor gene by thyroid hormone during Xenopus laevis metamorphosis. 1999, Pubmed , Xenbase
Glass, The coregulator exchange in transcriptional functions of nuclear receptors. 2000, Pubmed
Griffith, Knock-in mouse model for resistance to thyroid hormone (RTH): an RTH mutation in the thyroid hormone receptor beta gene disrupts cochlear morphogenesis. 2002, Pubmed
Grimaldi, High-throughput sequencing will metamorphose the analysis of thyroid hormone receptor function during amphibian development. 2013, Pubmed , Xenbase
Hadj-Sahraoui, Hypothyroidism prolongs mitotic activity in the post-natal mouse brain. 2000, Pubmed
Hasebe, Epithelial-connective tissue interactions induced by thyroid hormone receptor are essential for adult stem cell development in the Xenopus laevis intestine. 2011, Pubmed , Xenbase
Hasebe, Thyroid hormone-induced cell-cell interactions are required for the development of adult intestinal stem cells. 2013, Pubmed , Xenbase
Havis, Unliganded thyroid hormone receptor is essential for Xenopus laevis eye development. 2006, Pubmed , Xenbase
Havis, Metamorphic T3-response genes have specific co-regulator requirements. 2003, Pubmed , Xenbase
Howdeshell, A model of the development of the brain as a construct of the thyroid system. 2002, Pubmed
Hsia, Involvement of chromatin and histone acetylation in the regulation of HIV-LTR by thyroid hormone receptor. 2001, Pubmed , Xenbase
Jones, Multiple N-CoR complexes contain distinct histone deacetylases. 2001, Pubmed , Xenbase
Jones, The thyroid hormone receptor beta gene: structure and functions in the brain and sensory systems. 2003, Pubmed
Jones, N-CoR-HDAC corepressor complexes: roles in transcriptional regulation by nuclear hormone receptors. 2003, Pubmed , Xenbase
Kanamori, The regulation of thyroid hormone receptor beta genes by thyroid hormone in Xenopus laevis. 1992, Pubmed , Xenbase
Lazar, Thyroid hormone receptors: multiple forms, multiple possibilities. 1993, Pubmed
Lei, Efficient targeted gene disruption in Xenopus embryos using engineered transcription activator-like effector nucleases (TALENs). 2012, Pubmed , Xenbase
Lei, Generation of gene disruptions by transcription activator-like effector nucleases (TALENs) in Xenopus tropicalis embryos. 2013, Pubmed , Xenbase
Mai, Thyroid hormone receptor alpha is a molecular switch of cardiac function between fetal and postnatal life. 2004, Pubmed
Mansouri, Follicular cells of the thyroid gland require Pax8 gene function. 1998, Pubmed
Matsuda, Contrasting effects of two alternative splicing forms of coactivator-associated arginine methyltransferase 1 on thyroid hormone receptor-mediated transcription in Xenopus laevis. 2007, Pubmed , Xenbase
Matsuda, Novel functions of protein arginine methyltransferase 1 in thyroid hormone receptor-mediated transcription and in the regulation of metamorphic rate in Xenopus laevis. 2009, Pubmed , Xenbase
Matsuda, An essential and evolutionarily conserved role of protein arginine methyltransferase 1 for adult intestinal stem cells during postembryonic development. 2010, Pubmed , Xenbase
Matsuura, Liganded thyroid hormone receptor induces nucleosome removal and histone modifications to activate transcription during larval intestinal cell death and adult stem cell development. 2012, Pubmed , Xenbase
Matsuura, Histone H3K79 methyltransferase Dot1L is directly activated by thyroid hormone receptor during Xenopus metamorphosis. 2012, Pubmed , Xenbase
McKenna, Nuclear receptors, coregulators, ligands, and selective receptor modulators: making sense of the patchwork quilt. 2001, Pubmed
Morreale de Escobar, Thyroid hormones in tissues from fetal and adult rats. 1994, Pubmed
Morvan Dubois, Deiodinase activity is present in Xenopus laevis during early embryogenesis. 2006, Pubmed , Xenbase
Nagasawa, Thyroid hormone receptor beta 1 expression in developing mouse limbs and face. 1997, Pubmed
Nakajima, Dual mechanisms governing muscle cell death in tadpole tail during amphibian metamorphosis. 2003, Pubmed , Xenbase
Ng, A thyroid hormone receptor that is required for the development of green cone photoreceptors. 2001, Pubmed
Ng, A protective role for type 3 deiodinase, a thyroid hormone-inactivating enzyme, in cochlear development and auditory function. 2009, Pubmed
Paul, Distinct expression profiles of transcriptional coactivators for thyroid hormone receptors during Xenopus laevis metamorphosis. 2003, Pubmed , Xenbase
Paul, Tissue- and gene-specific recruitment of steroid receptor coactivator-3 by thyroid hormone receptor during development. 2005, Pubmed , Xenbase
Paul, SRC-p300 coactivator complex is required for thyroid hormone-induced amphibian metamorphosis. 2007, Pubmed , Xenbase
Paul, Coactivator recruitment is essential for liganded thyroid hormone receptor to initiate amphibian metamorphosis. 2005, Pubmed , Xenbase
Pei, Thyroid hormone receptor repression is linked to type I pneumocyte-associated respiratory distress syndrome. 2011, Pubmed
Puzianowska-Kuznicka, Both thyroid hormone and 9-cis retinoic acid receptors are required to efficiently mediate the effects of thyroid hormone on embryonic development and specific gene regulation in Xenopus laevis. 1997, Pubmed , Xenbase
Rachez, Mediator complexes and transcription. 2001, Pubmed
Ranjan, Transcriptional repression of Xenopus TR beta gene is mediated by a thyroid hormone response element located near the start site. 1994, Pubmed , Xenbase
Refetoff, Familial syndrome combining deaf-mutism, stuppled epiphyses, goiter and abnormally high PBI: possible target organ refractoriness to thyroid hormone. 1967, Pubmed
Sachs, Unliganded thyroid hormone receptor function: amphibian metamorphosis got TALENs. 2015, Pubmed , Xenbase
Sachs, Nuclear receptor corepressor recruitment by unliganded thyroid hormone receptor in gene repression during Xenopus laevis development. 2002, Pubmed , Xenbase
Sachs, Dual functions of thyroid hormone receptors during Xenopus development. 2000, Pubmed , Xenbase
Sachs, Targeted chromatin binding and histone acetylation in vivo by thyroid hormone receptor during amphibian development. 2000, Pubmed , Xenbase
Santos, Labile proteins are necessary for T3 induction of growth hormone mRNA in normal rat pituitary and rat pituitary tumor cells. 1987, Pubmed
Sato, A role of unliganded thyroid hormone receptor in postembryonic development in Xenopus laevis. 2007, Pubmed , Xenbase
Schreiber, Diverse developmental programs of Xenopus laevis metamorphosis are inhibited by a dominant negative thyroid hormone receptor. 2001, Pubmed , Xenbase
Schreiber, Tadpole skin dies autonomously in response to thyroid hormone at metamorphosis. 2003, Pubmed , Xenbase
Shi, The development of the adult intestinal stem cells: Insights from studies on thyroid hormone-dependent amphibian metamorphosis. 2011, Pubmed , Xenbase
Shi, Tadpole competence and tissue-specific temporal regulation of amphibian metamorphosis: roles of thyroid hormone and its receptors. 1996, Pubmed , Xenbase
Shi, Unliganded thyroid hormone receptor regulates metamorphic timing via the recruitment of histone deacetylase complexes. 2013, Pubmed , Xenbase
Shi, Thyroid hormone receptor actions on transcription in amphibia: The roles of histone modification and chromatin disruption. 2012, Pubmed
Tata, Early metamorphic competence of Xenopus larvae. 1968, Pubmed , Xenbase
Tata, Gene expression during metamorphosis: an ideal model for post-embryonic development. 1993, Pubmed
Tomita, Recruitment of N-CoR/SMRT-TBLR1 corepressor complex by unliganded thyroid hormone receptor for gene repression during frog development. 2004, Pubmed , Xenbase
Tsai, Molecular mechanisms of action of steroid/thyroid receptor superfamily members. 1994, Pubmed
Wang, Developmental regulation and function of thyroid hormone receptors and 9-cis retinoic acid receptors during Xenopus tropicalis metamorphosis. 2008, Pubmed , Xenbase
Wong, Coordinated regulation of and transcriptional activation by Xenopus thyroid hormone and retinoid X receptors. 1995, Pubmed , Xenbase
Wong, A role for nucleosome assembly in both silencing and activation of the Xenopus TR beta A gene by the thyroid hormone receptor. 1995, Pubmed , Xenbase
Yaoita, A correlation of thyroid hormone receptor gene expression with amphibian metamorphosis. 1990, Pubmed , Xenbase
Yen, Physiological and molecular basis of thyroid hormone action. 2001, Pubmed
You, The interaction between nuclear receptor corepressor and histone deacetylase 3 regulates both positive and negative thyroid hormone action in vivo. 2010, Pubmed
Zhang, The mechanism of action of thyroid hormones. 2000, Pubmed