Document Detail


Unliganded thyroid hormone receptor α controls developmental timing in Xenopus tropicalis.
MedLine Citation:
PMID:  25456066     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 two 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 implicated a role of unliganded TR during vertebrate development. On the other hand, it has been difficult to study the role of unliganded TR during development in mammals due to 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 TALENs (transcriptional activator like effector nucleases) 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 have not only 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.
Authors:
Luan Wen; Yun-Bo Shi
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-12-2
Journal Detail:
Title:  Endocrinology     Volume:  -     ISSN:  1945-7170     ISO Abbreviation:  Endocrinology     Publication Date:  2014 Dec 
Date Detail:
Created Date:  2014-12-2     Completed Date:  -     Revised Date:  2014-12-3    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  en20141439     Citation Subset:  -    
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