Unliganded thyroid hormone receptor is essential for Xenopus laevis eye development.
Thyroid hormone receptors generally activate transcription of target genes in the presence of thyroid hormone (T(3)) and repress their transcription in its absence. Here, we investigated the role of unliganded thyroid hormone receptor (TR) during vertebrate development using an amphibian model. Previous studies led to the hypothesis that before production of endogenous T(3), the presence of unliganded receptor is essential for premetamorphic tadpole growth. To test this hypothesis, we generated a Xenopus laevis TR beta mutant construct ineffective for gene repression owing to impaired corepressor NCoR recruitment. Overexpression by germinal transgenesis of the mutant receptor leads to lethality during early development with numerous defects in cranio-facial and eye development. These effects correlate with TR expression profiles at these early stages. Molecular analysis of transgenic mutants reveals perturbed expression of genes involved in eye development. Finally, treatment with iopanoic acid or NH-3, modulators of thyroid hormone action, leads to abnormal eye development. In conclusion, the data reveal a role of unliganded TR in eye development.
Havis
Emmanuelle
E
UMR5166 CNRS, USM-501 Muséum National d'Histoire Naturelle, Dépt. Régulation, Développement et Diversité Moléculaire, Paris, France.
Le Mevel
Sébastien
S
Morvan Dubois
Ghislaine
G
Shi
De-Li
DL
Scanlan
Thomas S
TS
Demeneix
Barbara A
BA
Sachs
Laurent M
LM
D000818:Animals; D003287:Contrast Media / Q000494:pharmacology; D005123:Eye / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics; D007480:Iopanoic Acid / Q000494:pharmacology; D008024:Ligands; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000378:metabolism*; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis
D003287:Contrast Media; D008024:Ligands; D009687:Nuclear Proteins; D011988:Receptors, Thyroid Hormone; D029867:Xenopus Proteins; D007480:Iopanoic Acid