Quantitation of endogenous thyroid hormone receptors α and β during embryogenesis and metamorphosis in Xenopus laevis (original) (raw)
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Amphibian metamorphosis as a model for the developmental actions of thyroid hormone
Molecular and Cellular Endocrinology, 2006
Thyroid hormone (TH) elicits multiple physiological actions in vertebrates from fish to man. These actions can be divided into two broad categories: those where the hormone regulates developmental processes and those that involve actions in the adult organism. Amphibian metamorphosis is a most dramatic example of extensive morphological, biochemical and cellular changes occurring during post-embryonic development, which is obligatorily initiated and sustained by TH. It is, therefore, an ideal model system to understand the action of the hormone. Each tissue of the frog tadpole responds differently to TH, ranging from altered gene expression, morphogenesis, tissue re-structuring and extensive cell death, according to a developmental programme set in place before the thyroid gland begins to secrete the hormone. The key element determining the response to the hormone is the nuclear thyroid hormone receptor (TR). As in most vertebrates, there are two thyroid hormone receptors, TR␣ and TR, which repress transcription in the absence of the ligand and whose concentration in the tissues is directly modulated by the hormone itself. In Xenopus, biochemical and in situ techniques have shown that the amount of TR mRNA and protein are elevated 50-100 times during TH-induced metamorphic climax. This phenomenon of "autoinduction" of receptor is also seen with developmental or inductive processes regulated by other hormones acting through nuclear receptors. It is possible that receptor upregulation may be a pre-requisite for hormonal response. Recent molecular and cell biological studies have suggested that TRs function as multimeric complexes with other nuclear or chromatin proteins, such as co-repressors and co-activators, to regulate the structure of the chromatin, and thereby determine the transcription of the receptor-specified target gene. There is evidence that this may also be so for thyroid hormone regulated transcription during amphibian metamorphosis.
Genes to Cells, 2012
During amphibian metamorphosis, a series of dynamic changes occur in a predetermined order. Hind limb morphogenesis begins in response to low levels of thyroid hormone (TH) in early prometamorphosis, but tail muscle cell death is delayed until climax, when TH levels are high. It takes about 20 days for tadpoles to grow from early prometamorphosis to climax. To study the molecular basis of the timing of tissue-specific transformations, we introduced thyroid hormone receptor (TR) expression constructs into tail muscle cells of Xenopus tadpoles. The TR-transfected tail muscle cells died upon exposure to a low level of thyroxine (T4). This cell death was suggested to be mediated by type 2 iodothyronine deiodinase (D2) that converts T4 to T3-the more active form of TH. D2 mRNA was induced in the TR-overexpressing cells by low levels of TH. D2 promoter contains a TH-response element (TRE) with a lower affinity for TR. These results show that the TR transfection confers the ability to respond to physiological concentrations of TH at early prometamorphosis to tail muscle cells through D2 activity and promotes TH signaling. We propose the positive feedback loop model to amplify the cell's ability to respond to low levels of T4.
Mechanisms of thyroid hormone receptor action during development: Lessons from amphibian studies
Biochimica et Biophysica Acta (BBA) - General Subjects, 2013
Background: Thyroid hormone (TH) receptor (TR) plays critical roles in vertebrate development. However, the in vivo mechanism of TR action remains poorly explored. Scope of review: 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. Major conclusion: 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. General significance: 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.
Gene expression changes at metamorphosis induced by thyroid hormone in Xenopus laevis tadpoles
Developmental Biology, 2006
Thyroid hormone (TH) controlled gene expression profiles have been studied in the tail, hind limb and brain tissues during TH-induced and spontaneous Xenopus laevis metamorphosis. Amplified cRNA probes mixed with a universal standard were hybridized to a set of 21,807-sense strand 60-mer oligonucleotides on each slide representing the entries in X. laevis UniGene Build 48. Most of the up-regulated genes in hind limb and brain are the same. This reflects in part the fact that the initial response to TH induction in both tissues is cell proliferation. A large number of up-regulated genes in the limb and brain programs encode common components of the cell cycle, DNA and RNA metabolism, transcription and translation. Notch is one of the few genes that is differentially expressed exclusively in the brain in the first 48 h of TH induction studied in these experiments. The TH-induced gene expression changes in the tail are different from the limb and brain programs. Distinct muscle and fibroblast programs were identified in the tail. Dying muscle fibers in tail (marked by active caspase-3) up-regulate a group of genes that include proteolytic enzymes. At the climax of metamorphosis, tail muscle down-regulates more than half of the genes that encode the glycolytic enzymes in the cytoplasm and the tricarboxylic acid pathway and all five complexes of the electron transport system in mitochondria. These changes in gene expression precede the activation of caspase-3. Some of these same energy metabolism-related genes are up-regulated in the limb and brain programs by TH. A prominent feature of the tail fibroblasts is the down-regulation of several collagen and other extra cellular matrix genes and the up-regulation of hydrolytic enzymes that are responsible for dissolving the notochord and resorbing the tail.
Dual functions of thyroid hormone receptors during Xenopus development
Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology, 2000
Thyroid hormone (TH) plays a causative role in anuran metamorphosis. This effect is presumed to be manifested through the regulation of gene expression by TH receptors (TRs). TRs can act as both activators and repressors of a TH-inducible gene depending upon the presence and absence of TH, respectively. We have been investigating the roles of TRs during Xenopus lae6is development, including premetamorphic and metamorphosing stages. In this review, we summarize some of the studies on the TRs by others and us. These studies reveal that TRs have dual functions in frog development as reflected in the following two aspects. First, TRs function initially as repressors of TH-inducible genes in premetamorphic tadpoles to prevent precocious metamorphosis, thus ensuring a proper period of tadpole growth, and later as activators of these genes to activate the metamorphic process. Second, TRs can promote both cell proliferation and apoptosis during metamorphosis, depending upon the cell type in which they are expressed.
Endocrinology
Thyroid hormone (TH) binds TH receptor α (TRα) and β (TRβ) to induce amphibian metamorphosis. Whereas TH signaling has been well studied, functional differences between TRα and TRβ during this process have not been characterized. To understand how each TR contributes to metamorphosis, we generated TRα- and TRβ-knockout tadpoles of Xenopus tropicalis and examined developmental abnormalities, histology of the tail and intestine, and messenger RNA expression of genes encoding extracellular matrix–degrading enzymes. In TRβ-knockout tadpoles, tail regression was delayed significantly and a healthy notochord was observed even 5 days after the initiation of tail shortening (stage 62), whereas in the tails of wild-type and TRα-knockout tadpoles, the notochord disappeared after ∼1 day. The messenger RNA expression levels of genes encoding extracellular matrix–degrading enzymes (MMP2, MMP9TH, MMP13, MMP14, and FAPα) were obviously reduced in the tail tip of TRβ-knockout tadpoles, with the sho...
Xenopus laevis as a model for studying thyroid hormone signalling: From development to metamorphosis
Molecular and Cellular Endocrinology, 2008
Please cite this article as: Morvan-Dubois, G., Demeneix, B.A., Sachs, L.M., Xenopus laevis as a model for studying thyroid hormone signalling: From development to metamorphosis, Molecular and Cellular Endocrinology (2007), A c c e p t e d M a n u s c r i p t 1 Xenopus laevis as a model for studying thyroid hormone signalling: from development to metamorphosis. Summary 150 words Introduction: Xenopus leavis and thyroid hormone signalling.
Developmentally regulated thyroid hormone distributor proteins in marsupials, a reptile, and fish
AJP: Regulatory, Integrative and Comparative Physiology, 2005
Developmentally regulated thyroid hormone distributor You might find this additional info useful... 45 articles, 14 of which you can access for free at: This article cites http://ajpregu.physiology.org/content/288/5/R1264.full#ref-list-1 1 other HighWire-hosted articles: This article has been cited by http://ajpregu.physiology.org/content/288/5/R1264#cited-by including high resolution figures, can be found at: Updated information and services http://ajpregu.physiology.org/content/288/5/R1264.full can be found at: and Comparative Physiology American Journal of Physiology -Regulatory, Integrative about Additional material and information http://www.the-aps.org/publications/ajpregu