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Journal articles on the topic 'Xenopus laevis – Metamorphosis'

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Published: 4 June 2021

Last updated: 17 February 2022

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1

Pronych, Scott, and Richard Wassersug. "Lung use and development in Xenopus laevis tadpoles." Canadian Journal of Zoology 72, no. 4 (April 1, 1994): 738–43. http://dx.doi.org/10.1139/z94-099.

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Shortly after hatching, Xenopus laevis tadpoles fill their lungs with air. We examined the role played by early lung use in these organisms, since they are able to respire with both their lungs and their gills. We investigated the effect on X. laevis development when the larvae were prevented from inflating their lungs, and whether early lung use influenced the size of the lungs or the tadpole's ability to metamorphose. Tadpoles that were denied access to air had lungs one-half the size of those of controls. This difference in lung size was too large to be explained merely by a stretching of the lung due to inflation. The longer tadpoles were denied access to air, the longer they took to metamorphose, and their probability of completing metamorphosis diminished. One tadpole raised throughout its larval life without access to air successfully metamorphosed but had abnormal, solidified lungs and an enlarged heart. Collectively, these experiments demonstrate that early lung use in tadpoles is important in determining both ultimate lung size and the probability of successfully metamorphosing. Lung use during early larval development in X. laevis is not absolutely necessary for survival through metamorphosis, but its absence severely handicaps growth.

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2

Mukhi, Sandeep, Liquan Cai, and Donald D. Brown. "Gene switching at Xenopus laevis metamorphosis." Developmental Biology 338, no. 2 (February 2010): 117–26. http://dx.doi.org/10.1016/j.ydbio.2009.10.041.

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3

Rose, Matthew F., and Susan R. Rose. "Melatonin accelerates metamorphosis in Xenopus laevis." Journal of Pineal Research 24, no. 2 (March 1998): 90–95. http://dx.doi.org/10.1111/j.1600-079x.1998.tb00372.x.

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4

Stolow, M. A., D. D. Bauzon, J. Li, T. Sedgwick, V. C. Liang, Q. A. Sang, and Y. B. Shi. "Identification and characterization of a novel collagenase in Xenopus laevis: possible roles during frog development." Molecular Biology of the Cell 7, no. 10 (October 1996): 1471–83. http://dx.doi.org/10.1091/mbc.7.10.1471.

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Matrix metalloproteinases (MMPs) participate in extracellular matrix remodeling and degradation and have been implicated in playing important roles during organ development and pathological processes. Although it has been hypothesized for > 30 years that collagenase activities are responsible for collagen degradation during tadpole tail resorption, none of the previously cloned amphibian MMPs have been biochemically demonstrated to be collagenases. Here, we report a novel matrix metalloproteinase gene from metamorphosing Xenopus laevis tadpoles. In vitro biochemical studies demonstrate that this Xenopus enzyme is an interstitial collagenase and has an essentially identical enzymatic activity toward a collagen substrate as the human interstitial collagenase. Sequence comparison of this enzyme to other known MMPs suggests that the Xenopus collagenase is not a homologue of any known collagenases but instead represents a novel collagenase, Xenopus collagenase-4 (xCol4, MMP-18). Interestingly, during development, xCol4 is highly expressed only transiently in whole animals, at approximately the time when tadpole feeding begins, suggesting a role during the maturation of the digestive tract. More importantly, during metamorphosis, xCol4 is regulated in a tissue-dependent manner. High levels of its mRNA are present as the tadpole tail resorbs. Similarly, its expression is elevated during hindlimb morphogenesis and intestinal remodeling. In addition, when premetamorphic tadpoles are treated with thyroid hormone, the causative agent of metamorphosis, xCol4 expression is induced in the tail. These results suggest that xCol4 may facilitate larval tissue degeneration and adult organogenesis during amphibian metamorphosis.

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5

Das, B., and D. D. Brown. "Controlling transgene expression to study Xenopus laevis metamorphosis." Proceedings of the National Academy of Sciences 101, no. 14 (March 26, 2004): 4839–42. http://dx.doi.org/10.1073/pnas.0401011101.

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6

Schreiber, A. M., L. Cai, and D. D. Brown. "Remodeling of the intestine during metamorphosis of Xenopus laevis." Proceedings of the National Academy of Sciences 102, no. 10 (February 28, 2005): 3720–25. http://dx.doi.org/10.1073/pnas.0409868102.

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7

Slater, Bethany J., Karen J. Liu, Matthew D. Kwan, Natalina Quarto, and Michael T. Longaker. "Tissue turnover in the Xenopus laevis skull during metamorphosis." Journal of the American College of Surgeons 207, no. 3 (September 2008): S65. http://dx.doi.org/10.1016/j.jamcollsurg.2008.06.160.

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8

Walsh, P., R. Downie, and P. Monaghan. "Plasticity of the duration of metamorphosis in Xenopus laevis." Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology 146, no. 4 (April 2007): S176. http://dx.doi.org/10.1016/j.cbpa.2007.01.376.

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9

Fort, Douglas J., Robert L. Rogers, Joseph W. Gorsuch, Lisa T. Navarro, Robert Peter, and James R. Plautz. "Triclosan and Anuran Metamorphosis: No Effect on Thyroid-Mediated Metamorphosis in Xenopus laevis." Toxicological Sciences 113, no. 2 (November 16, 2009): 392–400. http://dx.doi.org/10.1093/toxsci/kfp280.

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10

Asada-Kubota, M. "A monoclonal antibody specific for an epidermal cell antigen of Xenopus laevis: electron microscopic observations using a gold-labeling method." Journal of Histochemistry & Cytochemistry 36, no. 5 (May 1988): 515–21. http://dx.doi.org/10.1177/36.5.3356895.

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A monoclonal antibody (EPI-1), raised against the supernatant of a homogenate of Xenopus laevis larvae at the tailbud stage (stage 36/37), interacts specifically with a 250 KD epidermal antigen of Xenopus. An immunocytochemical gold-labeling technique was used to investigate changes in antigen distribution during epidermal development of Xenopus laevis. Specific immunolabeling was initially detected over the endoplasmic reticulum in the outer epithelial cells of the late gastrula stage (stage 12.5). After the early neurula stage (stage 13), immunolabeling appeared over moderately electron-dense bodies (these bodies disappear after stage 29), and also over the apical cell surface and adjacent cytoplasm of all the outer epithelial cells. During metamorphosis, labeling decreased and disappeared after stage 62, as the superficial layer had peeled off. These data suggest that the antigen is useful as a marker of general differentiation in studies of epidermal development during the embryonic and larval stages of Xenopus laevis.

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11

Grimaldi, S., A. Lisi, S. Reiti, V. Manni, M. Ledda, and L. Giuliani. "Influence of 50-Hz Electromagnetic Field on Anurian (Xenopus laevis) Metamorphosis." Scientific World JOURNAL 4 (2004): 41–47. http://dx.doi.org/10.1100/tsw.2004.177.

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In this study, we show the effect of a 1-mT magnetic field AC at 50 Hz onXenopuslaevis tadpole populations. In the course of a 65-day exposure to the field, tadpole survival showed a small, but significant, decrease (p < 0.0004), together with a striking parallel 6-day shift in tadpole maturation frequency and a significant impairment of their metamorphosis. Particularly, metamorphosis was successful for 85% of individuals in the unirradiated tadpole population and for 45% of individuals in the irradiated tadpole population, respectively.

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12

Lim, Wayland, Eric S. Neff, and J. David Furlow. "The mouse muscle creatine kinase promoter faithfully drives reporter gene expression in transgenicXenopus laevis." Physiological Genomics 18, no. 1 (June 17, 2004): 79–86. http://dx.doi.org/10.1152/physiolgenomics.00148.2003.

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Developing Xenopus laevis experience two periods of muscle differentiation, once during embryogenesis and again at metamorphosis. During metamorphosis, thyroid hormone induces both muscle growth in the limbs and muscle death in the tail. In mammals, the muscle creatine kinase (MCK) gene is activated during the differentiation from myoblasts to myocytes and has served as both a marker for muscle development and to drive transgene expression in transgenic mice. Transcriptional control elements are generally highly conserved throughout evolution, potentially allowing mouse promoter use in transgenic X. laevis. This paper compares endogenous X. laevis MCK gene expression and the mouse MCK (mMCK) promoter driving a green fluorescent protein reporter in transgenic X. laevis. The mMCK promoter demonstrated strong skeletal muscle-specific transgene expression in both the juvenile tadpole and adult frog. Therefore, our results clearly demonstrate the functional conservation of regulatory sequences in vertebrate muscle gene promoters and illustrate the utility of using X. laevis transgenesis for detailed comparative study of mammalian promoter activity in vivo.

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13

Okada, Morihiro, Thomas C. Miller, Liezhen Fu, and Yun-Bo Shi. "Direct Activation of Amidohydrolase Domain-Containing 1 Gene by Thyroid Hormone Implicates a Role in the Formation of Adult Intestinal Stem Cells During Xenopus Metamorphosis." Endocrinology 156, no. 9 (June 18, 2015): 3381–93. http://dx.doi.org/10.1210/en.2015-1190.

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The T3-dependent anuran metamorphosis resembles postembryonic development in mammals, the period around birth when plasma T3 levels peak. In particular, the remodeling of the intestine during metamorphosis mimics neonatal intestinal maturation in mammals when the adult intestinal epithelial self-renewing system is established. We have been using intestinal metamorphosis to investigate how the organ-specific adult stem cells are formed during vertebrate development. Early studies in Xenopus laevis have shown that this process involves complete degeneration of the larval epithelium and de novo formation of adult stem cells. A tissue-specific microarray analysis of intestinal gene expression during Xenopus laevis metamorphosis has identified a number of candidate stem cell genes. Here we have carried out detailed analyses of one such gene, amidohydrolase domain containing 1 (AMDHD1) gene, which encodes an enzyme in the histidine catabolic pathway. We show that AMDHD1 is exclusively expressed in the proliferating adult epithelial stem cells during metamorphosis with little expression in other intestinal tissues. We further provide evidence that T3 activates AMDHD1 gene expression directly at the transcription level through T3 receptor binding to the AMDHD1 gene in the intestine. In addition, we have reported earlier that histidine ammonia-lyase gene, another gene in histidine catabolic pathway, is similarly regulated by T3 in the intestine. These results together suggest that histidine catabolism plays a critical role in the formation and/or proliferation of adult intestinal stem cells during metamorphosis.

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14

Furlow, J. David, and Eric S. Neff. "A developmental switch induced by thyroid hormone: Xenopus laevis metamorphosis." Trends in Endocrinology & Metabolism 17, no. 2 (March 2006): 40–47. http://dx.doi.org/10.1016/j.tem.2006.01.007.

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15

Mukhi, Sandeep, Marko E. Horb, and Donald D. Brown. "Remodeling of insulin producing β-cells during Xenopus laevis metamorphosis." Developmental Biology 328, no. 2 (April 2009): 384–91. http://dx.doi.org/10.1016/j.ydbio.2009.01.038.

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16

Rot-Nikcevic, I. "Arrested development in Xenopus laevis tadpoles: how size constrains metamorphosis." Journal of Experimental Biology 207, no. 12 (May 15, 2004): 2133–45. http://dx.doi.org/10.1242/jeb.01002.

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17

Huang, H., and D. D. Brown. "Prolactin is not a juvenile hormone in Xenopus laevis metamorphosis." Proceedings of the National Academy of Sciences 97, no. 1 (January 4, 2000): 195–99. http://dx.doi.org/10.1073/pnas.97.1.195.

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18

Ruben, Laurens N., Ronaldo T. de Leon, Rachel O. Johnson, Sallie Bowman, and Richard E. Clothier. "Interleukin-2-induced mortality during the metamorphosis of Xenopus laevis." Immunology Letters 51, no. 3 (July 1996): 157–61. http://dx.doi.org/10.1016/0165-2478(96)02540-0.

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19

Li, Meng, Chuyan Cao, Shuying Li, Wenjun Gui, and Guonian Zhu. "Thyroid endocrine disruption of azocyclotin to Xenopus laevis during metamorphosis." Environmental Toxicology and Pharmacology 43 (April 2016): 61–67. http://dx.doi.org/10.1016/j.etap.2016.02.015.

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20

Itoh, K., A. Yamashita, and H. Y. Kubota. "The expression of epidermal antigens in Xenopus laevis." Development 104, no. 1 (September 1, 1988): 1–14. http://dx.doi.org/10.1242/dev.104.1.1.

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Five kinds of monoclonal antibodies that are specific for the epidermis of Xenopus embryos were produced. Epidermis-specific antibodies were used to investigate the spatial and temporal expressions of epidermal antigens during embryonic and larval development. The cells that were recognized by the antibodies at the larval stage are as follows: all of the outer epidermal cells and cement gland cells were recognized by the antibody termed XEPI-1, all of the outer and inner epidermal cells, except the cement gland cells, were recognized by XEPI-2 antibody, the large mucus granules and the apical side of the outer epidermal cells, except for the ciliated epidermal cells, were recognized by XEPI-3 antibody, the large mucus granules and basement membrane were recognized by XEPI-4 antibody, and the small mucus granules contained in the outer epidermal cells as well as extracellular matrices were recognized by the antibody termed XEPI-5. All of the epidermal antigens, except XEPI-4, were first detected in the epidermal region of the late gastrula or early neurula. The XEPI-4 antigen was first detected in stage-26 tail-bud embryos. None of these antigens were expressed by the neural tissues at any time during embryonic development. Only the XEPI-2 antigen continued to be expressed after metamorphosis, while the expression of the other antigens disappeared during or before metamorphosis. The specificity of the antibodies allowed us to classify the epidermal cells into four types in early epidermal development. The four types of epidermal cells are (1) the outer epidermal cells that contain small mucus granules, (2) the ciliated epidermal cells, (3) the outer epidermal cells that contain large mucus granules and (4) the inner sensorial cells.

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21

Robert, J., J. Wolff, H. Jijakli, J. D. Graf, F. Karch, and H. R. Kobel. "Developmental expression of the creatine kinase isozyme system of Xenopus: maternally derived CK-IV isoform persists far beyond the degradation of its maternal mRNA and into the zygotic expression period." Development 108, no. 3 (March 1, 1990): 507–14. http://dx.doi.org/10.1242/dev.108.3.507.

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The differential expression of the multilocus CK isozyme system throughout development of the two Xenopus species X. laevis and X. borealis was investigated. A cDNA containing the nearly complete coding sequence of the CK-IV subunit of X. laevis was isolated and sequenced. Early development of X. laevis proceeds with a stock of maternally derived CK-IV/IV isozyme. While the mRNA declines rapidly after fertilization and disappears before neurulation, maternal CK-IV/IV isozyme is active far beyond the onset of zygotic expression and is still detectable when tadpoles start feeding. Zygotic expression of CK-IV begins after neurulation, at stage 22/24, and seems to start simultaneously with that of another gene, CK-III. Modulation in the expression of these two genes and the appearance of two other isoforms, the CK-I and CK-II/III isozymes, take place during development in a tissue-specific manner. During metamorphosis, the CK phenotypes of eyes and skeletal musculature undergo additional changes. The final adult pattern only appears several weeks after metamorphosis. The presumed orthologous CK isozymes of X. borealis show a developmental profile similar to that of X. laevis, except that CK-II/II is equally present in oocytes and during early development, in addition to CK-IV/IV isozyme. These results show that the expression of each of the four CK genes of Xenopus is under differential developmental control.

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22

Ruben, Laurens N., Richard H. Clothier, and Michael Balls. "Cancer Resistance in Amphibians." Alternatives to Laboratory Animals 35, no. 5 (October 2007): 463–70. http://dx.doi.org/10.1177/026119290703500514.

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While spontaneous tumours may occasionally develop in inbred and isogenic strains of Xenopus laevis, the South African clawed toad, they are extremely rare in natural and laboratory populations. Only two amphibian neoplasms, the renal adenocarcinoma of Rana pipiens and the lymphosarcoma of Xenopus laevis, have been extensively explored. Amphibians are resistant to the development of neo-plasia, even following exposure to “direct-acting” chemical carcinogens such as N-methyl- N-nitrosourea, that are highly lymphotoxic, thus diminishing immune reactivity. Regenerative capacity in adults, and a dramatic metamorphosis which remodels much of the larval body to produce the adult form, are unique to amphibian vertebrates, and the control mechanisms involved may protect against cancer. For example, naturally rising corticosteroid titres during metamorphosis will impair some T-cell functions, and the removal of T-regulatory (suppressor) functions inhibits the induction of altered-self tolerance. Altered-self tolerance is not as effectively induced in adult Xenopus laevis as in mammals, so cancer cells with new antigenicity are more likely be rejected in amphibians. Amphibian immunocytes tend to undergo apoptosis readily in vitro, and, unlike mammalian immunocytes, undergo apoptosis without entering the cell cycle. Cells not in the cell cycle that die from nuclear damage (apoptosis), will have no opportunity to express genetic instability leading to cell transformation. We suggest that all these factors, rather than any one of them, may reduce susceptibility to cancer in amphibians.

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23

Levi, G., F. Broders, D. Dunon, G. M. Edelman, and J. P. Thiery. "Thyroxine-dependent modulations of the expression of the neural cell adhesion molecule N-CAM during Xenopus laevis metamorphosis." Development 108, no. 4 (April 1, 1990): 681–92. http://dx.doi.org/10.1242/dev.108.4.681.

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During amphibian metamorphosis, a complete remodeling of the phenotype takes place under complex hormonal control whose final effectors are thyroid hormones. This process implies the activation of coordinated programs of cell death, proliferation, migration, adhesion and differentiation. Inasmuch as the neural cell adhesion molecule N-CAM is thought to play a central role in the control of morphogenetic processes, we have studied by immunohistofluorescence and immunoblots the patterns of expression of N-CAM at different stages of Xenopus laevis metamorphosis. A scan was made of all major organs and appendages. Before the metamorphic climax, all neuronal cell bodies and processes express high levels of N-CAM. During the metamorphic climax, N-CAM expression decreases sharply on the cell bodies and processes of the peripheral nervous system (PNS) but remains high in the central nervous system (CNS). Towards the end of metamorphosis, the PNS and spinal nerves are virtually negative for N-CAM while the CNS is still positive. The optic and olfactory nerves, although myelinated, are still strongly positive for N-CAM. The lens and olfactory epithelia express N-CAM throughout metamorphosis. In the brain. N-CAM is present at all times as three polypeptides of 180, 140, and 120 X 10(3) Mr; before metamorphosis some of the N-CAM is in its polysialylated form. During metamorphosis and the subsequent growth of the animal, the amount of N-CAM decreases gradually. In all polypeptides, the polysialylated form is the first to disappear. Cardiac muscle expresses high level of N-CAM from its first formation throughout metamorphosis; in contrast, the level of N-CAM in skeletal muscle is high in newly formed muscles, but decreases rapidly after myoblast fusion. The liver of adult Xenopus contains large amounts of a 160 X 10(3) polypeptide that is recognized by polyclonal and monoclonal antibodies against N-CAM. cDNA probes of Xenopus brain N-CAM recognize major transcripts of 9.2, 3.8 and 3.3 kb in Xenopus liver mRNA; these bands are different in size from those recognized in brain mRNA (9.5, 4.2 and 2.2 kb). Premetamorphic liver does not express the 160 X 10(3) form of N-CAM, which can be first detected at stage 59 and persists then through all the life of the animal. Expression of N-CAM in the liver can be induced in premetamorphic animals (stage 51–52) by a 48 h treatment with thyroxine. All hepatocytes are responsive.(ABSTRACT TRUNCATED AT 400 WORDS)

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24

Mawaribuchi, Shuuji, Kei Tamura, Saori Okano, Shutaro Takayama, Yoshio Yaoita, Tadayoshi Shiba, Nobuhiko Takamatsu, and Michihiko Ito. "Tumor Necrosis Factor-α Attenuates Thyroid Hormone-Induced Apoptosis in Vascular Endothelial Cell Line XLgoo Established from Xenopus Tadpole Tails." Endocrinology 149, no. 7 (April 10, 2008): 3379–89. http://dx.doi.org/10.1210/en.2007-1591.

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Amphibian metamorphosis induced by T3 involves programmed cell death and the differentiation of various types of cells in degenerated and reconstructed tissues. However, the signaling pathway that directs the T3-dependent cell-fate determinations remains unclear. TNF-α is a pleiotropic cytokine that affects diverse cellular responses. Engagement of TNF-α with its receptor (TNFR1) causes intracellular apoptotic and/or survival signaling. To investigate TNF signaling functions during anuran metamorphosis, we first identified Xenopus laevis orthologs of TNF (xTNF)-α and its receptor. We found that xTNF-α activated nuclear factor-κB in X. laevis A6 cells through the Fas-associated death domain and receptor-interacting protein 1. Interestingly, xTNF-α mRNA in blood cells showed prominent expression at prometamorphosis during metamorphosis. Next, to elucidate the apoptotic and/or survival signaling induced by xTNF-α in an in vitro model of metamorphosis, we established a vascular endothelial cell line, XLgoo, from X. laevis tadpole tail. XLgoo cells formed actin stress fibers and elongated in response to xTNF-α. T3 induced apoptosis in these cells, but the addition of xTNF-α blocked the T3-induced apoptosis. In addition, treatment of the cells with T3 for 2 d induced the expression of thyroid hormone receptor-β and caspase-3, and this thyroid hormone receptor-β induction was drastically repressed by xTNF-α. Furthermore, in organ culture of the tail, xTNF-α significantly attenuated the tail degeneration induced by T3. These findings suggested that xTNF-α could protect vascular endothelial cells from apoptotic cell death induced by T3 during metamorphosis and thereby participate in the regulation of cell fate.

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25

Krain, LP, and RJ Denver. "Developmental expression and hormonal regulation of glucocorticoid and thyroid hormone receptors during metamorphosis in Xenopus laevis." Journal of Endocrinology 181, no. 1 (April 1, 2004): 91–104. http://dx.doi.org/10.1677/joe.0.1810091.

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Corticosteroids, the primary circulating vertebrate stress hormones, are known to potentiate the actions of thyroid hormone in amphibian metamorphosis. Environmental modulation of the production of stress hormones may be one way that tadpoles respond to variation in their larval habitat, and thus control the timing of metamorphosis. Thyroid hormone and corticosteroids act through structurally similar nuclear receptors, and interactions at the transcriptional level could lead to regulation of common pathways controlling metamorphosis. To better understand the roles of corticosteroids in amphibian metamorphosis we analyzed the developmental and hormone-dependent expression of glucocorticoid receptor (GR) mRNA in the brain (diencephalon), intestine and tail of Xenopus laevis tadpoles. We compared the expression patterns of GR with expression of thyroid hormone receptor beta (TRbeta). In an effort to determine the relationship between nuclear hormone receptor expression and levels of ligand, we also analyzed changes in whole-body content of 3,5,3'-triiodothyronine (T(3)), thyroxine, and corticosterone (CORT). GR transcripts of 8, 4 and 2 kb were detected in all tadpole tissues, but only the 4 and 2 kb transcripts could be detected in embryos. The level of GR mRNA was low during premetamorphosis in the brain but increased significantly during prometamorphosis, remained at a constant level throughout metamorphosis, and increased to its highest level in the juvenile frog. GR mRNA level in the intestine remained relatively constant, but increased in the tail throughout metamorphosis, reaching a maximum at metamorphic climax. The level of GR mRNA was increased by treatment with CORT in the intestine but not in the brain or tail. TRbeta mRNA level increased in the brain, intestine and tail during metamorphosis and was induced by treatment with T(3). Analysis of possible crossregulatory relationships between GRs and TRs showed that GR mRNA was upregulated by exogenous T(3) (50 nM) in the tail but downregulated in the brain of premetamorphic tadpoles. Exogenous CORT (100 nM) upregulated TRbeta mRNA in the intestine. Our findings provide evidence for tissue-specific positive, negative and crossregulation of nuclear hormone receptors during metamorphosis of X. laevis. The synergy of CORT with T(3) on tadpole tail resorption may depend on the accelerated accumulation of GR transcripts in this tissue during metamorphosis, which may be driven by rising plasma thyroid hormone titers.

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26

Ueno, Tomoya, Akinori Ishihara, Shinomi Yagi, Toru Koike, Kiyoshi Yamauchi, and Nobuyoshi Shiojiri. "Histochemical Analyses of Biliary Development During Metamorphosis of Xenopus laevis Tadpoles." Zoological Science 32, no. 1 (January 1, 2015): 88. http://dx.doi.org/10.2108/zs140104.

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27

Buckbinder, L., and D. D. Brown. "Expression of the Xenopus laevis prolactin and thyrotropin genes during metamorphosis." Proceedings of the National Academy of Sciences 90, no. 9 (May 1, 1993): 3820–24. http://dx.doi.org/10.1073/pnas.90.9.3820.

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28

Brown, D. D., Z. Wang, J. D. Furlow, A. Kanamori, R. A. Schwartzman, B. F. Remo, and A. Pinder. "The thyroid hormone-induced tail resorption program during Xenopus laevis metamorphosis." Proceedings of the National Academy of Sciences 93, no. 5 (March 5, 1996): 1924–29. http://dx.doi.org/10.1073/pnas.93.5.1924.

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29

OKA, T., O. TOOI, N. MITSUI, M. MIYAHARA, Y. OHNISHI, M. TAKASE, A. KASHIWAGI, T. SHINKAI, N. SANTO, and T. IGUCHI. "Effect of atrazine on metamorphosis and sexual differentiation in Xenopus laevis." Aquatic Toxicology 87, no. 4 (May 30, 2008): 215–26. http://dx.doi.org/10.1016/j.aquatox.2008.02.009.

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30

Levi, G., D. Ginsberg, J. M. Girault, I. Sabanay, J. P. Thiery, and B. Geiger. "EP-cadherin in muscles and epithelia of Xenopus laevis embryos." Development 113, no. 4 (December 1, 1991): 1335–44. http://dx.doi.org/10.1242/dev.113.4.1335.

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EP-cadherin is a novel Xenopus Ca+2-dependent adhesion molecule, which shares comparable homology with mouse E- and P-cadherins (Ginsberg, De Simone and Geiger; 1991, Development 111, 315–325). We report here the patterns of expression of this molecule in Xenopus laevis embryos at different developmental stages ranging from cleavage to postmetamorphic. EP-cadherin is already expressed in the oocyte and egg and can then be detected in close association with the membrane of all blastomeres up to late blastula stages. Starting at late gastrula stages, the level of EP-cadherin expression increases sharply in non-neural ectodermal cells, in the somites and in the notochord; it persists in endodermal cells and decreases rapidly in all migratory cells. During neurulation the level of EP-cadherin expression declines gradually in the nervous system and is undetectable here throughout later development except in the optic nerve and in the neural part of the olfactory organ. This pattern continues during later development so that in the tailbud stage and up to metamorphosis the most prominent staining is detected in the epidermis and skeletal muscle. After metamorphosis, the molecule gradually disappears from the muscle tissue and the major site of expression remains the skin. EP-cadherin is invariably present in close association with the cell membrane. In the muscle it is associated with the sarcolemma at regions of myoblast-myoblast or myotube-myotube contact. In epidermal cells, EP-cadherin is usually coexpressed with E-cadherin. Yet, while E-cadherin staining is always restricted to the basolateral aspects of the cells, EP-cadherin is often distributed throughout the plasmalemma including the apical surface.

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31

Hilken, G., J. Dimigen, and F. Iglauer. "Growth of Xenopus laevis under different laboratory rearing conditions." Laboratory Animals 29, no. 2 (April 1, 1995): 152–62. http://dx.doi.org/10.1258/002367795780740276.

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Since the European frogs ( Rana spp.) have fallen under the German endangered species regulation, Xenopus laevis (South African Clawed Frog) is being used increasingly in animal research and education. Optimal growth rates and homogeneity of groups have not necessarily been attained as little statistical analysis of growth data has been available. Following metamorphosis, an as yet not understood variability of growth is exhibited by X. laevis. In this study the effect of environmental factors on this variability was determined. Feeding, population density, background colouring, water temperature, the availability of hiding places, water level and water care were each examined separately. Development of body weight and body length were recorded. A definite correlation between the feeding programme, population density, cover and water care on the one hand and growth on the other were seen. Of lesser importance were water temperature, water level and background colouring. The observed variability of growth is assumed to also be of ethological origin.

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Fukuzawa, T., and H. Ide. "Further studies on the melanophores of periodic albino mutant of Xenopus laevis." Development 91, no. 1 (February 1, 1986): 65–78. http://dx.doi.org/10.1242/dev.91.1.65.

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It is still unknown why dermal melanophores disappear during larval development, and why no or very few epidermal melanophores appear during and after metamorphosis, in Xenopus laevis showing periodic albinism (ap). To elucidate these points, we investigated (1) the occurrence of depigmentation in mutant (ap/ap) melanophores during in vitro proliferation and (2) the incidence of melanophore differentiation from mutant melanoblasts in the skin in vitro. During in vitro proliferation of mutant melanophores, ap-type melanosomes decreased in number gradually and instead the number of premelanosomes increased in the cells, which caused depigmentation at the light microscopic level in the culture. Depigmentation was observed only in mutant melanophores, and not in wild-type (+/+) melanophores. These results suggest that autonomous depigmentation of mutant dermal melanophores is the cause of the disappearance of these cells in vivo. Dopa-positive melanoblasts were demonstrated in both wild-type and mutant skins. However, the melanoblasts of metamorphosed mutant froglets did not differentiate in vitro, while those of wild-type froglets did. These results suggest that mutant melanoblasts in the skin of froglets lose the potency to differentiate into melanophores, and that this causes the lack of mutant melanophores in the froglets. The site of action of the ap gene is also discussed.

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Mathisen, P. M., and L. Miller. "Thyroid hormone induces constitutive keratin gene expression during Xenopus laevis development." Molecular and Cellular Biology 9, no. 5 (May 1989): 1823–31. http://dx.doi.org/10.1128/mcb.9.5.1823.

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We have used in vitro explant cultures of Xenopus laevis skin to investigate the role that the thyroid hormone triiodothyronine (T3) plays in activating the 63-kilodalton (kDa) keratin genes. The activation of these genes in vivo requires two distinct steps, one independent of T3 and one dependent on T3. In this report we have shown that the same two steps are required to fully activate the 63-kDa keratin genes in skin explant cultures, and we have characterized the T3-mediated step in greater detail. Unlike the induction of transcription by T3 or steroid hormones in adult tissues, there was a long latent period of approximately 2 days between the addition of T3 to skin cultures and an increase in concentration of keratin mRNA. While the T3 induction of 63-kDa keratin gene transcription cannot occur until age 48, a short transient exposure of stage 40 skin cultures to T3 resulted in high-level expression of these genes 5 days later, when normal siblings had reached stage 48. This result indicates that T3 induces a stable change in epidermal cells which can be expressed much later, after extensive cell proliferation has occurred in the absence of T3. Once the 63-kDa keratin genes were induced, they were stably expressed, and by the end of metamorphosis T3 had no further effect on their expression. The results suggest that T3 induces constitutive expression of the 63-kDa keratin genes during metamorphosis.

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Mathisen, P. M., and L. Miller. "Thyroid hormone induces constitutive keratin gene expression during Xenopus laevis development." Molecular and Cellular Biology 9, no. 5 (May 1989): 1823–31. http://dx.doi.org/10.1128/mcb.9.5.1823-1831.1989.

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We have used in vitro explant cultures of Xenopus laevis skin to investigate the role that the thyroid hormone triiodothyronine (T3) plays in activating the 63-kilodalton (kDa) keratin genes. The activation of these genes in vivo requires two distinct steps, one independent of T3 and one dependent on T3. In this report we have shown that the same two steps are required to fully activate the 63-kDa keratin genes in skin explant cultures, and we have characterized the T3-mediated step in greater detail. Unlike the induction of transcription by T3 or steroid hormones in adult tissues, there was a long latent period of approximately 2 days between the addition of T3 to skin cultures and an increase in concentration of keratin mRNA. While the T3 induction of 63-kDa keratin gene transcription cannot occur until age 48, a short transient exposure of stage 40 skin cultures to T3 resulted in high-level expression of these genes 5 days later, when normal siblings had reached stage 48. This result indicates that T3 induces a stable change in epidermal cells which can be expressed much later, after extensive cell proliferation has occurred in the absence of T3. Once the 63-kDa keratin genes were induced, they were stably expressed, and by the end of metamorphosis T3 had no further effect on their expression. The results suggest that T3 induces constitutive expression of the 63-kDa keratin genes during metamorphosis.

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Hammoud, Lamis, Logan A. Walsh, and Sashko Damjanovski. "Cloning and developmental characterization of Xenopus laevis membrane type-3 matrix metalloproteinase (MT3-MMP)." Biochemistry and Cell Biology 84, no. 2 (April 1, 2006): 167–77. http://dx.doi.org/10.1139/o05-175.

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Proper extracellular matrix (ECM) remodeling, mediated by matrix metalloproteinases (MMPs), is crucial for the development and survival of multicellular organisms. Full-length Xenopus laevis membrane type-3 matrix metallo proteinase (MT3-MMP) was amplified by PCR and cloned from a stage 28 Xenopus head cDNA library. A comparison of the derived Xenopus MT3-MMP protein sequence to that of other vertebrates revealed 86% identity with human and mouse and 85% identity with chicken. The expression profile of MT3-MMP was examined during Xenopus embryogenesis: MT3-MMP transcripts were first detected at the later stages of development and were localized to dorsal and anterior structures. During metamorphosis and in the adult frog, MT3-MMP expression was restricted to specific tissues and organs. Treatment of Xenopus embryos with lithium chloride (LiCl), ultraviolet irradiation (UV), or retinoic acid (RA) revealed that MT3-MMP levels increased with LiCl-dorsalizing treatments and decreased with UV-ventralizing and RA-anterior neural truncating treatments. Overexpression of MT3-MMP through RNA injections led to dose-dependent developmental abnormalities and death. Moreover, MT3-MMP overexpression resulted in neural and head structure abnormalities, as well as truncated axes. Taken together, these results indicate that MT3-MMP expression in Xenopus is spatially and temporally restricted. Furthermore, deregulation of MT3-MMP during early embryogenesis has detrimental effects on development.Key words: Xenopus laevis, MT3-MMP, development, ECM, dorsalization, ventralization.

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Kay, B. K., L. M. Schwartz, U. Rutishauser, T. H. Qiu, and H. B. Peng. "Patterns of N-CAM expression during myogenesis in Xenopus laevis." Development 103, no. 3 (July 1, 1988): 463–71. http://dx.doi.org/10.1242/dev.103.3.463.

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The neural cell adhesion molecule (N-CAM) is seen in the membrane of nerves and muscles from several vertebrate species. Using indirect immunofluorescence, we have examined the expression of this protein during embryonic and postembryonic myogenesis in the African clawed frog, Xenopus laevis. While good staining for N-CAM was seen in neuronal tissues at all stages examined, no staining of embryonic muscle was observed, including both mononucleated and polynucleated myoblasts. In contrast, limb muscles formed at metamorphosis showed strong expression of N-CAM. The developing limb muscles eventually lose their N-CAM, but will reexpress it dramatically when denervated. These observations suggest that myogenesis programs executed at different stages of development can display distinct patterns of N-CAM expression.

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Marshall, Lindsey N., Céline J. Vivien, Fabrice Girardot, Louise Péricard, Pierluigi Scerbo, Karima Palmier, Barbara A. Demeneix, and Laurent Coen. "Stage-dependent cardiac regeneration in Xenopus is regulated by thyroid hormone availability." Proceedings of the National Academy of Sciences 116, no. 9 (February 12, 2019): 3614–23. http://dx.doi.org/10.1073/pnas.1803794116.

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Despite therapeutic advances, heart failure is the major cause of morbidity and mortality worldwide, but why cardiac regenerative capacity is lost in adult humans remains an enigma. Cardiac regenerative capacity widely varies across vertebrates. Zebrafish and newt hearts regenerate throughout life. In mice, this ability is lost in the first postnatal week, a period physiologically similar to thyroid hormone (TH)-regulated metamorphosis in anuran amphibians. We thus assessed heart regeneration in Xenopus laevis before, during, and after TH-dependent metamorphosis. We found that tadpoles display efficient cardiac regeneration, but this capacity is abrogated during the metamorphic larval-to-adult switch. Therefore, we examined the consequence of TH excess and deprivation on the efficiently regenerating tadpole heart. We found that either acute TH treatment or blocking TH production before resection significantly but differentially altered gene expression and kinetics of extracellular matrix components deposition, and negatively impacted myocardial wall closure, both resulting in an impeded regenerative process. However, neither treatment significantly influenced DNA synthesis or mitosis in cardiac tissue after amputation. Overall, our data highlight an unexplored role of TH availability in modulating the cardiac regenerative outcome, and present X. laevis as an alternative model to decipher the developmental switches underlying stage-dependent constraint on cardiac regeneration.

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Mukhi, Sandeep, Liquan Cai, and Donald D. Brown. "Gene-switching, cell-switching and cell-reprogramming during metamorphosis in Xenopus laevis." Developmental Biology 331, no. 2 (July 2009): 499–500. http://dx.doi.org/10.1016/j.ydbio.2009.05.427.

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39

Fort, D. J., R. L. Rogers, S. Pawlowski, and S. Champ. "Triclosan Does Not Affect Thyroid-Mediated Metamorphosis in Xenopus laevis--Additional Data." Toxicological Sciences 119, no. 2 (November 12, 2010): 419–22. http://dx.doi.org/10.1093/toxsci/kfq344.

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40

Hasebe, Takashi, and Atsuko Ishizuya-Oka. "Stem Cell Development in the Small Intestinal Epithelium during Xenopus laevis Metamorphosis." Nihon Ika Daigaku Igakkai Zasshi 8, no. 1 (2012): 4–5. http://dx.doi.org/10.1272/manms.8.4.

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41

Gibbs, Kurt M., Sridar V. Chittur, and Ben G. Szaro. "Metamorphosis and the regenerative capacity of spinal cord axons in Xenopus laevis." European Journal of Neuroscience 33, no. 1 (November 9, 2010): 9–25. http://dx.doi.org/10.1111/j.1460-9568.2010.07477.x.

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42

Clothier, R. H., L. N. Ruben, M. Balls, and L. Greenhalgh. "Morphological and immunological changes in the spleen of Xenopus laevis during metamorphosis." Research in Immunology 142, no. 4 (January 1991): 360–62. http://dx.doi.org/10.1016/0923-2494(91)90092-w.

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43

Jolivet-Jaudet, Geneviève, and Jeanine Leloup-Hâtey. "Corticosteroid binding in plasma of Xenopus laevis. Modifications during metamorphosis and growth." Journal of Steroid Biochemistry 25, no. 3 (September 1986): 343–50. http://dx.doi.org/10.1016/0022-4731(86)90245-1.

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44

Banker, D. E., J. Bigler, and R. N. Eisenman. "The thyroid hormone receptor gene (c-erbA alpha) is expressed in advance of thyroid gland maturation during the early embryonic development of Xenopus laevis." Molecular and Cellular Biology 11, no. 10 (October 1991): 5079–89. http://dx.doi.org/10.1128/mcb.11.10.5079.

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The c-erbA proto-oncogene encodes the thyroid hormone receptor, a ligand-dependent transcription factor which plays an important role in vertebrate growth and development. To define the role of the thyroid hormone receptor in developmental processes, we have begun studying c-erbA gene expression during the ontogeny of Xenopus laevis, an organism in which thyroid hormone has well-documented effects on morphogenesis. Using polymerase chain reactions (PCR) as a sensitive assay of specific gene expression, we found that polyadenylated erbA alpha RNA is present in Xenopus cells at early developmental stages, including the fertilized egg, blastula, gastrula, and neurula. By performing erbA alpha-specific PCR on reverse-transcribed RNAs from high-density sucrose gradient fractions prepared from early-stage embryos, we have demonstrated that these erbA transcripts are recruited to polysomes. Therefore, erbA is expressed in Xenopus development prior to the appearance of the thyroid gland anlage in tailbud-stage embryos. This implies that erbA alpha/thyroid hormone receptors may play ligand-independent roles during the early development of X. laevis. Quantitative PCR revealed a greater than 25-fold range in the steady-state levels of polyadenylated erbA alpha RNA across early stages of development, as expressed relative to equimolar amounts of total embryonic RNA. Substantial increases in the levels of erbA alpha RNA were noted at stages well after the onset of zygotic transcription at the mid-blastula transition, with accumulation of erbA alpha transcripts reaching a relative maximum in advance of metamorphosis. We also show that erbA alpha RNAs are expressed unequally across Xenopus neural tube embryos. This differential expression continues through later stages of development, including metamorphosis. This finding suggests that erbA alpha/thyroid hormone receptors may play roles in tissue-specific processes across all of Xenopus development.

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Banker, D. E., J. Bigler, and R. N. Eisenman. "The thyroid hormone receptor gene (c-erbA alpha) is expressed in advance of thyroid gland maturation during the early embryonic development of Xenopus laevis." Molecular and Cellular Biology 11, no. 10 (October 1991): 5079–89. http://dx.doi.org/10.1128/mcb.11.10.5079-5089.1991.

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The c-erbA proto-oncogene encodes the thyroid hormone receptor, a ligand-dependent transcription factor which plays an important role in vertebrate growth and development. To define the role of the thyroid hormone receptor in developmental processes, we have begun studying c-erbA gene expression during the ontogeny of Xenopus laevis, an organism in which thyroid hormone has well-documented effects on morphogenesis. Using polymerase chain reactions (PCR) as a sensitive assay of specific gene expression, we found that polyadenylated erbA alpha RNA is present in Xenopus cells at early developmental stages, including the fertilized egg, blastula, gastrula, and neurula. By performing erbA alpha-specific PCR on reverse-transcribed RNAs from high-density sucrose gradient fractions prepared from early-stage embryos, we have demonstrated that these erbA transcripts are recruited to polysomes. Therefore, erbA is expressed in Xenopus development prior to the appearance of the thyroid gland anlage in tailbud-stage embryos. This implies that erbA alpha/thyroid hormone receptors may play ligand-independent roles during the early development of X. laevis. Quantitative PCR revealed a greater than 25-fold range in the steady-state levels of polyadenylated erbA alpha RNA across early stages of development, as expressed relative to equimolar amounts of total embryonic RNA. Substantial increases in the levels of erbA alpha RNA were noted at stages well after the onset of zygotic transcription at the mid-blastula transition, with accumulation of erbA alpha transcripts reaching a relative maximum in advance of metamorphosis. We also show that erbA alpha RNAs are expressed unequally across Xenopus neural tube embryos. This differential expression continues through later stages of development, including metamorphosis. This finding suggests that erbA alpha/thyroid hormone receptors may play roles in tissue-specific processes across all of Xenopus development.

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Sundqvist, Monika. "Developmental changes of purinergic control of intestinal motor activity during metamorphosis in the African clawed frog, Xenopus laevis." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 292, no. 5 (May 2007): R1916—R1925. http://dx.doi.org/10.1152/ajpregu.00785.2006.

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Little is known about the purinergic regulation of intestinal motor activity in amphibians. Purinergic control of intestinal motility is subject to changes during development in mammals. The aim of this study was to investigate purinergic control of intestinal smooth muscle in the amphibian Xenopus laevis and explore possible changes in this system during the developmental phase of metamorphosis. Effects of purinergic compounds on mean force and contraction frequency in intestinal circular muscle strips from prometamorphic, metamorphic, and juvenile animals were investigated. Before metamorphosis, low concentrations of ATP reduced motor activity, whereas the effects were reversed at higher concentrations. ATP-induced relaxation was not inhibited by the P2-receptor antagonist pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS) but was blocked by the ecto-nucleotidase inhibitor 6- N, N-diethyl-d-β,γ-dibromomethylene ATP ( ARL67256 ), indicating that an ATP-derived metabolite mediated the relaxation response at this stage. Adenosine induced relaxation before, during, and after metamorphosis, which was blocked by the A1-receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX). The stable ATP-analog adenosine 5′-[γ-thio]-triphosphate (ATPγS) and 2-methylthioATP (2-MeSATP) elicited contractions in the circular muscle strips in prometamorphic tadpoles. However, in juvenile froglets, 2-MeSATP caused relaxation, as did ATPγS at low concentrations. The P2Y11/P2X1-receptor antagonist NF157 antagonized the ATPγS-induced relaxation. The P2X-preferring agonist α-β-methyleneadenosine 5′-triphosphate (α-β-MeATP) evoked PPADS-sensitive increases in mean force at all stages investigated. This study demonstrates the existence of an adenosine A1-like receptor mediating relaxation and a P2X-like receptor mediating contraction in the X. laevis gut before, during, and after metamorphosis. Furthermore, the development of a P2Y11-like receptor-mediated relaxation during metamorphosis is shown.

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Kuiper, George G. J. M., Willem Klootwijk, Ghislaine Morvan Dubois, Olivier Destree, Veerle M. Darras, Serge Van der Geyten, Barbara Demeneix, and Theo J. Visser. "Characterization of Recombinant Xenopus laevis Type I Iodothyronine Deiodinase: Substitution of a Proline Residue in the Catalytic Center by Serine (Pro132Ser) Restores Sensitivity to 6-Propyl-2-Thiouracil." Endocrinology 147, no. 7 (July 1, 2006): 3519–29. http://dx.doi.org/10.1210/en.2005-0711.

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In frogs such as Rana and Xenopus, metamorphosis does not occur in the absence of a functional thyroid gland. Previous studies indicated that coordinated development in frogs requires tissue and stage-dependent type II and type III iodothyronine deiodinase expression patterns to obtain requisite levels of intracellular T3 in tissues at the appropriate stages of metamorphosis. No type I iodothyronine deiodinase (D1), defined as T4 or reverse T3 (rT3) outer-ring deiodinase (ORD) activity with Michaelis constant (Km) values in the micromolar range and sensitivity to 6-propyl-2-thiouracil (6-PTU), could be detected in tadpoles so far. We obtained a X. laevis D1 cDNA clone from brain tissue. The complete sequence of this clone (1.1 kb, including poly A tail) encodes an ORF of 252 amino acid residues with high homology to other vertebrate D1 enzymes. The core catalytic center includes a UGA-encoded selenocysteine residue, and the 3′ untranslated region (about 300 nt) contains a selenocysteine insertion sequence element. Transfection of cells with an expression vector containing the full-length cDNA resulted in generation of significant deiodinase activity in the homogenates. The enzyme displayed ORD activity with T4 (Km 0.5 μm) and rT3 (Km 0.5 μm) and inner-ring deiodinase activity with T4 (Km 0.4 μm). Recombinant Xenopus D1 was essentially insensitive to inhibition by 6-PTU (IC50 > 1 mm) but was sensitive to gold thioglucose (IC50 0.1 μm) and iodoacetate (IC50 10 μm). Because the residue 2 positions downstream from the selenocysteine is Pro in Xenopus D1 but Ser in all cloned PTU-sensitive D1 enzymes, we prepared the Pro132Ser mutant of Xenopus D1. The mutant enzyme showed strongly increased ORD activity with T4 and rT3 (Km about 4 μm) and was highly sensitive to 6-PTU (IC50 2 μm). Little native D1 activity could be detected in Xenopus liver, kidney, brain, and gut, but significant D1 mRNA expression was observed in juvenile brain and adult liver and kidney. These results indicate the existence of a 6-PTU-insensitive D1 enzyme in X. laevis tissues, but its role during tadpole metamorphosis remains to be defined.

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Li, Yan Chun, Clemens Bergwitz, Harald Jüppner, and Marie B. Demay. "Cloning and Characterization of the Vitamin D Receptor from Xenopus laevis*." Endocrinology 138, no. 6 (June 1, 1997): 2347–53. http://dx.doi.org/10.1210/endo.138.6.5210.

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Abstract The Vitamin D receptor (VDR), a member of the nuclear receptor superfamily, mediates the effects of 1,25-dihydroxyvitamin D3 on mineral ion homeostasis. Although the mammalian and avian VDRs have been extensively studied, little is known about the VDR in lower vertebrate species. To address this, we have isolated the Xenopus laevis VDR (xVDR) complementary DNA. Overall, the xVDR shares 79%, 73%, 73%, and 75% identity at the amino acid level with the chicken, mouse, rat, and human VDRs, respectively. The amino acid residues and subdomains important for DNA binding, hormone binding, dimerization, and transactivation are mostly conserved among all VDR species. The xVDR polypeptide can heterodimerize with the mouse retinoid X receptor α, bind to the rat osteocalcin vitamin D response element (VDRE), and induce vitamin D-dependent transactivation in transfected mammalian cells. Northern analysis reveals two xVDR messenger RNA species of 2.2 kb and 1.8 kb in stage 60 Xenopus tissues. In the adult, xVDR expression is detected in many tissues including kidney, intestine, skin, and bone. During Xenopus development, xVDR messenger RNA first appears at developmental stage 13 (preneurulation), increasing to maximum at stages 57–61 (metamorphosis). Our data demonstrate that, in Xenopus, VDR expression is developmentally regulated and that the vitamin D endocrine system is highly conserved during evolution.

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Fort, Douglas J., Michael B. Mathis, Warren Hanson, Chelsea E. Fort, Lisa T. Navarro, Robert Peter, Claudia Büche, Sabine Unger, Sascha Pawlowski, and James R. Plautz. "Triclosan and Thyroid-Mediated Metamorphosis in Anurans: Differentiating Growth Effects from Thyroid-Driven Metamorphosis in Xenopus laevis." Toxicological Sciences 121, no. 2 (March 23, 2011): 292–302. http://dx.doi.org/10.1093/toxsci/kfr069.

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50

Mengeling, Brenda J., Michael L. Goodson, and J. David Furlow. "RXR Ligands Modulate Thyroid Hormone Signaling Competence in Young Xenopus laevis Tadpoles." Endocrinology 159, no. 7 (May 11, 2018): 2576–95. http://dx.doi.org/10.1210/en.2018-00172.

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Abstract Appropriate thyroid hormone (TH) signaling through thyroid hormone receptors (TRs) is essential for vertebrate development. Amphibian metamorphosis is initiated and sustained through the action of TH on TRs, which are conserved across vertebrates. TRs heterodimerize with retinoid X receptors (RXRs) on thyroid hormone response elements (TREs) in the genome; however, in most cell line and adult animal studies, RXR ligands do not affect expression of TR target genes. We used a quantitative, precocious metamorphosis assay to interrogate the effects of the RXR agonist bexarotene (Bex) and the RXR antagonist UVI 3003 (UVI) on T3-induced resorption phenotypes in Xenopus laevis tadpoles 1 week postfertilization. Bex potentiated gill and tail resorption, and UVI abrogated T3 action. These results held in transgenic tadpoles bearing a TRE-driven luciferase reporter. Therefore, we used poly-A-primed RNA sequencing transcriptomic analysis to determine their effects on T3-induced gene expression. We also assayed the environmental pollutant tributyltin (TBT), which is an RXR agonist. We found that the proteases that carry out resorption were potentiated by Bex and TBT but were not significantly inhibited by UVI. However, several transcription factors from multiple families (sox4, fosl2, mxd1, mafb, nfib) were all inhibited by UVI and potentiated by Bex and TBT. All required T3 for induction. Time course analysis of gene expression showed that although the agonists could potentiate within 12 hours, the antagonist response lagged. These data indicate that the agonists and antagonist are not necessarily functioning through the same mechanism and suggest that RXR liganding may modulate TH competence in metamorphic signaling.

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