Expression of matrix metalloproteinase genes in regressing or remodeling organs during amphibian metamorphosis (original) (raw)
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Develop Growth Differ, 2007
Several matrix metalloproteinases (MMP) are induced by thyroid hormone (TH) during the climax of amphibian metamorphosis, and play a pivotal role in the remodeling intestine and the regressing tail and gills by degrading the extracellular matrix (ECM). We compared MMP gene expression levels precisely by the quantitative real time reverse transcription-polymerase chain reaction. The expression of MMP genes increases prominently at NF stages 60, 60-61, and 62 in the intestine, gills, and tail, respectively, when the drastic morphological change starts in each organ. The gene expression analysis in the TH-treated tadpoles and cell line revealed that MMP mRNAs are up-regulated in response to TH quickly within several hours to low levels and then increase in a day to high levels. All TH-induced MMP genes have thyroid hormone response elements (TREs). The presence of high affinity TREs in MMP genes correlates with the early TH-induction. Based on these results, we propose that TH stimulates the transcription of MMP genes through TREs within several hours to low levels, and then bring about the main increase of mRNAs by TH-induced transcriptional factors including TH receptor β in cell type-specific transcriptional environment.
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.
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.
Journal of Biological Chemistry, 2009
Thyroid hormone (T3) is essential for normal development and organ function throughout vertebrates. Its effects are mainly mediated through transcriptional regulation by T3 receptor (TR). The identification and characterization of the immediate early, direct target genes are thus of critical importance in understanding the molecular pathways induced by T3. Unfortunately, this has been hampered by the difficulty to study gene regulation by T3 in uterus-enclosed mammalian embryos. Here we used Xenopus metamorphosis as a model for vertebrate postembryonic development to identify direct T3 response genes in vivo. We took advantage of the ability to easily induce metamorphosis with physiological levels of T3 and to carry out microarray analysis in Xenopus laevis and genome-wide sequence analysis in Xenopus tropicalis. This allowed us to identify 188 up-regulated and 249 down-regulated genes by T3 in the absence of new protein synthesis in whole animals. We further provide evidence to show that these genes contain functional TREs that are bound by TR in tadpoles and that their promoters are regulated by TR in vivo. More importantly, gene ontology analysis showed that the direct up-regulated genes are enriched in categories important for transcriptional regulation and protein degradation-dependent signaling processes but not DNA replication. Our findings thus revealed the existence of interesting pathways induced by T3 at the earliest step of metamorphosis.
Development, Growth and Differentiation, 2005
During amphibian metamorphosis the digestive tract is extensively remodeled under the control of epithelialconnective tissue interactions. At the cellular level, larval epithelial cells undergo apoptosis, while a small number of stem cells appear, actively proliferate, and then differentiate to form adult epithelium that is analogous to its mammalian counterpart. Therefore the amphibian digestive tract is a unique model system for the study of postembryonic organ regeneration. As amphibian intestinal remodeling can be triggered by thyroid hormone (TH), the molecular mechanisms involved can be studied from the perspective of examining the expression cascade of TH response genes. A number of these genes have been isolated from the intestine of Xenopus laevis. Recent progress in the functional analysis of this cascade has shed light on key molecules in intestinal remodeling such as matrix metalloproteinase-11, sonic hedgehog, and bone morphogenetic protein-4. These genes are also thought to play key roles in organogenesis and/or homeostasis in both chick and mammalian digestive tract, suggesting the existence of conserved mechanisms underlying such events in terrestrial vertebrates. In this article, we review our recent findings in this field, focusing on the development of adult epithelium in the X. laevis intestine.
BioEssays, 1996
Amphibian metamorphosis is a post-embryonic process that systematically transforms different tissues in a tadpole. Thyroid hormone plays a causative role in this complex process by inducing a cascade of gene regulation. While natural metamorphosis does not occur until endogenous thyroid hormone has been synthesized, tadpoles are competent to respond to exogenous thyroid hormone shortly after hatching. In addition, even though the metamorphic transitions of individual organs are all controlled by thyroid hormone, each occurs at distinct developmental stages. Recent molecular studies suggest that this competence of premetamorphic tadpoles to respond to the hormone and the developmental stage-dependent regulation of tissue-specific transformations are determined in part by the levels of thyroid hormone receptors and the concentrations of cellular free thyroid hormone. In addition, at least two genes, encoding a cytosolic thyroid hormone binding protein and a 5-deiodinase, respectively, are likely to be critical players in regulating cellular free thyroid hormone concentrations. This review discusses how all of these molecular components coordinate to induce amphibian metamorphosis in a correct spatial and temporal manner. These studies provide us with general clues as to how and why tissues become Accepted
Amphibian metamorphosis as a model for studying the developmental actions of thyroid hormone
Biochimie, 1999
The thyroid hormones L-thyroxine and triiodo-L-thyronine have profound effects on postembryonic development of most vertebrates. Analysis of their action in mammals is vitiated by the exposure of the developing foetus to a number of maternal factors which do not allow one to specifically define the role of thyroid hormone (TH) or that of other hormones and factors that modulate its action. Amphibian metamorphosis is obligatorily dependent on TH which can initiate all the diverse physiological manifestations of this postembryonic developmental process (morphogenesis, cell death, re-structuring, etc.) in free-living embryos and larvae of most anurans. This article will first describe the salient features of metamorphosis and its control by TH and other hormones. Emphasis will be laid on the key role played by TH receptor (TR), in particular the phenomenon of TR gene autoinduction, in initiating the developmental action of TH. Finally, it will be argued that the findings on the control of amphibian metamorphosis enhance our understanding of the regulation of postembryonic development by TH in other vertebrate species. © Société française de biochimie et biologie moléculaire / Elsevier, Paris thyroid hormone / metamorphosis / postembryonic development / thyroid hormone receptor / autoinduction
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...