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Functional Cloning Using a Xenopus Oocyte Expression System
Published on: January 30, 2016
Unliganded thyroid hormone receptor is essential for Xenopus laevis eye development
Emmanuelle Havis1, Sébastien Le Mevel, Ghislaine Morvan Dubois
1UMR5166 CNRS, USM-501 Muséum National d'Histoire Naturelle, Dépt. Régulation, Développement et Diversité Moléculaire, Paris, France.
The EMBO Journal
|September 29, 2006
Summary
Unliganded thyroid hormone receptors are crucial for early vertebrate development, particularly eye formation. This study reveals their essential role before thyroid hormone (T3) production, impacting tadpole growth and development.
Area of Science:
- Developmental Biology
- Endocrinology
- Molecular Biology
Background:
- Thyroid hormone receptors (TRs) typically regulate gene transcription based on thyroid hormone (T3) presence.
- Unliganded TRs were hypothesized to be essential for premetamorphic tadpole growth before endogenous T3 production.
Purpose of the Study:
- To investigate the role of unliganded thyroid hormone receptors (TRs) during early vertebrate development.
- To test the hypothesis that unliganded TRs are essential for premetamorphic tadpole growth.
Main Methods:
- Generated a Xenopus laevis TR beta mutant construct unable to recruit corepressor NCoR for gene repression.
- Overexpressed the mutant receptor via germinal transgenesis in Xenopus embryos.
- Analyzed developmental defects, gene expression patterns, and effects of thyroid hormone action modulators.
Main Results:
- Overexpression of the mutant TR led to early developmental lethality with cranio-facial and eye defects.
- Perturbed expression of key genes involved in eye development was observed in transgenic mutants.
- Modulators of thyroid hormone action also resulted in abnormal eye development.
Conclusions:
- Unliganded thyroid hormone receptors play a critical, previously unrecognized role in eye development.
- This function is essential during early vertebrate development, prior to significant thyroid hormone production.
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