title: Mechanisms of thyroid hormone receptor action during development: lessons from amphibian studies.
abstract: BACKGROUND
  Thyroid hormone (TH) receptor (TR) plays critical roles in vertebrate development. However, the in vivo mechanism of TR action remains poorly explored.
  
  
  METHODS
  Frog metamorphosis is controlled by TH and mimics the postembryonic period in mammals when high levels of TH are also required. We review here some of the findings on the developmental functions of TH and TR and the associated mechanisms obtained from this model system.
  
  
  CONCLUSIONS
  A dual function model for TR in Anuran development was proposed over a decade ago. That is, unliganded TR recruits corepressors to TH response genes in premetamorphic tadpoles to repress these genes and prevent premature metamorphic changes. Subsequently, when TH becomes available, liganded TR recruits coactivators to activate these same genes, leading to metamorphic changes. Over the years, molecular and genetic approaches have provided strong support for this model. Specifically, it has been shown that unliganded TR recruits histone deacetylase containing corepressor complexes during larval stages to control metamorphic timing, while liganded TR recruits multiple histone modifying and chromatin remodeling coactivator complexes during metamorphosis. These complexes can alter chromatin structure via nucleosome position alterations or eviction and histone modifications to contribute to the recruitment of transcriptional machinery and gene activation.
  
  
  CONCLUSIONS
  The molecular mechanisms of TR action in vivo as revealed from studies on amphibian metamorphosis are very likely applicable to mammalian development as well. These findings provide a new perspective for understanding the diverse effects of TH in normal physiology and diseases caused by TH dysfunction. This article is part of a Special Issue entitled Thyroid hormone signalling.
authors.affiliation: Muséum National d'Histoire Naturelle, Dépt. Régulation Développement et Diversité Moléculaire, UMR7221 CNRS, Evolution des Régulations Endocriniennes, Section on thyroid hormone receptor function and mechanism of action, 57 rue Cuvier, 75231 Paris cedex 05, France.
authors.forename: Alexis
authors.initials: A
authors.lastname: Grimaldi
authors.forename: Nicolas
authors.initials: N
authors.lastname: Buisine
authors.forename: Thomas
authors.initials: T
authors.lastname: Miller
authors.forename: Yun-Bo
authors.initials: YB
authors.lastname: Shi
authors.forename: Laurent M
authors.initials: LM
authors.lastname: Sachs
mesh_terms: D000818:Animals; D056970:Co-Repressor Proteins / Q000235:genetics / Q000378:metabolism; D004827:Epilepsy; D018507:Gene Expression Regulation, Developmental; D008675:Metamorphosis, Biological; D011988:Receptors, Thyroid Hormone / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction; D013963:Thyroid Hormones / Q000235:genetics* / Q000378:metabolism*; D014981:Xenopus
chemical_list: D056970:Co-Repressor Proteins; D011988:Receptors, Thyroid Hormone; D013963:Thyroid Hormones