Transgenic analysis reveals that thyroid hormone receptor is sufficient to mediate the thyroid hormone signal in frog metamorphosis

Daniel R. Buchholz, Akihiro Tomita, Liezhen Fu, Bindu D. Paul, Yun Bo Shi

研究成果: Article査読

112 被引用数 (Scopus)

抄録

Thyroid hormone (T3) has long been known to be important for vertebrate development and adult organ function. Whereas thyroid hormone receptor (TR) knockout and transgenic studies of mice have implicated TR involvement in mammalian development, the underlying molecular bases for the resulting plienotypes remain to be determined in vivo, especially considering that T3 is known to have both genomic, i.e., through TRs, and nongenomic efects on cells. Amphibian metamorphosis is an excellent model for studying the role of TR in vertebrate development because of its total dependence on T3. Here we investigated the role of TR in metamorphosis by developing a dominant positive mutant thyroid hormone receptor (dpTR). In the frog oocyle transcription system, dpTR bound a T3-responsive promoter and activated the promoter independently of T3. Transgenic expression of dpTR under the control of a heat shock-inducible promoter in premetamorphic tadpoles led to precocious metamorphic transformations. Molecular analyses showed that dpTR induced metamorphosis by specifically binding to known T3 target genes, leading to increased local histone acetylation and gene activation, similar to T3-bound TR during natural metamorphosis. Our experiments indicated that the metamorphic role of T3 is through genomic action of the hormone, at least on the developmental parameters tested. They further provide the first example where TR is shown to mediate directly and sufficiently these developmental effects of T3 in individual organs by regulating target gene expression in these organs.

本文言語English
ページ(範囲)9026-9037
ページ数12
ジャーナルMolecular and Cellular Biology
24
20
DOI
出版ステータスPublished - 10-2004
外部発表はい

All Science Journal Classification (ASJC) codes

  • 分子生物学
  • 細胞生物学

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