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Stephen D Roper - One of the best experts on this subject based on the ideXlab platform.
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uptake and release of neurotransmitter candidates 3h serotonin 3h glutamate and 3h γ aminobutyric acid in taste buds of the mudpuppy Necturus maculosus
The Journal of Comparative Neurology, 1998Co-Authors: Joan Welton, Takatoshi Nagai, Stephen D Roper, Rona J. DelayAbstract:Neurotransmitters in vertebrate taste buds have not yet been identified with confidence. Serotonin, glutamate, and γ-aminobutyric acid (GABA) have been postulated, but the evidence is incomplete. We undertook an autoradiographic study of [3H]serotonin, [3H]glutamate, and [3H]GABA uptake in lingual epithelium from the amphibian, Necturus maculosus, to determine whether taste bud cells would accumulate and release these substances. Lingual epithelium containing taste buds was incubated in low concentrations (0.4–6 μM) of these tritiated transmitter candidates and the tissue was processed for light microscopic autoradiography. Merkel-like basal taste cells accumulated [3H]serotonin. When the tissue was treated with 40 mM K+ after incubating the tissue in [3H]serotonin, cells released the radiolabelled transmitter. Furthermore, depolarization (KCl)-induced release of [3H]serotonin was Ca-dependent: if Ca2+ was reduced to 0.4 mM and 20 mM Mg2+ added to the high K+ bathing solution, Merkel-like basal cells did not release [3H]serotonin. In contrast, [3H]glutamate was taken up by several cell types, including non-sensory epithelial cells, Schwann cells, and some taste bud cells. [3H]glutamate was not released by depolarizing the tissue with 40 mM K+. [3H]GABA uptake was also widespread, but did not occur in taste bud cells. [3H]GABA accumulated in non-sensory epithelial cells and Schwann cells. These data support the hypothesis that serotonin is a neurotransmitter or neuromodulator released by Merkel-like basal cells in Necturus taste buds. The data do not support (nor rule out) a neurotransmitter role for glutamate or GABA in taste buds. J. Comp. Neurol. 392:199–208, 1998. © 1998 Wiley-Liss, Inc.
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serotonin modulates voltage dependent calcium current in Necturus taste cells
Journal of Neurophysiology, 1997Co-Authors: Rona J. Delay, Stephen D Roper, Sue C KinnamonAbstract:Delay, Rona J., Sue C. Kinnamon, and Stephen D. Roper. Serotonin modulates voltage-dependent calcium current in Necturus taste cells. J. Neurophysiol. 77: 2515–2524, 1997. Necturus taste buds conta...
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membrane properties and cell ultrastructure of taste receptor cells in Necturus lingual slices
Journal of Neurophysiology, 1996Co-Authors: Albertino Bigiani, Dae Joong Kim, Stephen D RoperAbstract:1. Whole cell patch-clamp recordings and electron micrographs were obtained from cells in Necturus taste buds in lingual slices to study their membrane properties and to correlate these properties ...
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reduction of electrical coupling between Necturus taste receptor cells a possible role in acid taste
Neuroscience Letters, 1994Co-Authors: Albertino Bigiani, Stephen D RoperAbstract:Cytoplasmic acidification in taste receptor cells is thought to be involved, at least in part, in acid taste transduction. Since in taste buds about 20% of the receptor cells are electrically coupled, we have tested whether reduction in intracellular pH affects these lateral synaptic interactions. By applying the patch clamp technique to a slice preparation of Necturus lingual epithelium, we found that electrical coupling between taste receptor cells was strongly reduced by cytoplasmic acidification. Therefore, electrical coupling in taste buds might be modified during acid stimulation.
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bidirectional synaptic transmission in Necturus taste buds
The Journal of Neuroscience, 1994Co-Authors: Douglas A Ewald, Stephen D RoperAbstract:Pairs of taste cells were impaled with intracellular recording microelectrodes in intact taste buds in slices of Necturus lingual epithelium. Applying short pulses of 140 mM KCl or 200 mM CaCl2 solutions to the apical pore elicited receptor potentials in taste receptor cells. Chemostimulation of receptor cells elicited postsynaptic responses in basal cells in the taste bud. Postsynaptic responses in basal cells had a threshold for activation and did not saturate with increasing doses of chemical stimulus applied to the receptor cells. We directly depolarized individual receptor cells and tested whether this would evoke postsynaptic responses in basal cells. Depolarizing receptor cells to approximately 0 mV evoked small depolarizing responses in basal cells in 16% of the experiments. The properties of these responses were consistent with their being mediated by a chemical synapse. A comparison of the responses in basal cells evoked by depolarizing single receptor cells, with responses evoked by stimulating the entire receptor cell population with KCl suggests that there is extensive synaptic convergence from receptor cells onto each basal cell. We also tested whether electrical excitation of basal cells would elicit (retrograde) synaptic responses in receptor cells. Single depolarizing pulses (up to 1 sec duration) applied to basal cells through the intracellular recording microelectrode never evoked synaptic responses in receptor cells. However, when repetitive electrical stimuli were applied to basal cells (four to six 1 sec depolarizations to approximately 0 mV every 12 sec) we observed prolonged effects on receptor cells in 11 of 23 experiments. These effects included an increase in the amplitude of receptor potentials elicited by KCI (mean +/- SD = +19 +/- 5%), an increase in membrane input resistance of receptor cells (+27 +/- 11%), and a hyperpolarization of receptor cells (3–10 mV). In control experiments, repetitive stimulation of one receptor cell never elicited such effects in another receptor cell. We investigated the possibility that serotonin (5-HT), released from basal cells, mediated the above modulatory effects on receptor cells. Bath-applied 5-HT (100 microM) mimicked the effects produced by repetitive basal cell stimulation (KCI responses increased by 23 +/- 12%; input resistance increased by 24 +/- 11%; hyperpolarization of 5–15 mV; N = 14). We conclude that basal cells release 5-HT onto adjacent taste receptor cells and that this enhances the electrotonic propagation of receptor potentials from the apical (chemosensitive) tip to the basal (synaptic) processes of receptor cells. The net effect is that activation of basal cells effectively increases the chemosensitivity of taste receptor cells.
Gabor Kottra - One of the best experts on this subject based on the ideXlab platform.
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protein kinase inhibitor h7 prevents the decrease of tight junction resistance induced by serosal ca2 removal in Necturus gallbladder epithelium
Cellular Physiology and Biochemistry, 1995Co-Authors: Gabor KottraAbstract:Changes of the tight junction resistance (Rj) of the Necturus gallbladder epithelium in response to Ca2+ removal from the bath solutions were investigated by conventional electrophysiological methods and two-dimensional cable analysis. Luminal superfusion with Ca2+-free solution left Rj almost unchanged, while serosal removal of Ca2+ induced a slow decrease of Rj from 155 ± 10 to 25 ± 6 Ωcm2 (n = 10) within 2 h. Simultaneously the apical membrane resistance decreased while the basolateral membrane resistance as well as the gap junction resistance increased. Application of the protein kinase inhibitor H7 (50 µmol/l) blocked these resistance changes. Similar protective effects of H7 on the transepithelial resistance (Rt) were previously observed on MDCK cells [Citi: J Cell Biol 1992; 117:169]. In contrast, 5 µmol/l chelerythrine chloride, a specific blocker of the protein kinase C, did not prevent the decrease of Rj induced by serosal removal of Ca2+. These results indicate that the integrity of the tight junctions of Necturus gallbladder epithelium depends on the serosal, but not on the luminal presence of Ca2+ and that the resistance decline includes a process that can be inhibited by H7, but not by chelerythrine chloride.
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calcium is not involved in the camp mediated stimulation of cl conductance in the apical membrane of Necturus gallbladder epithelium
Pflügers Archiv: European Journal of Physiology, 1995Co-Authors: Gabor KottraAbstract:The permeability properties of the forskolinstimulated Cl− conductance in the apical membrane of Necturus gallbladder epithelium and the possible participation of intracellular Ca2+ in its stimulation have been investigated. The anion selectivity sequence as derived from biionic potential measurements (SCN− > I− ≈ NO 3 − > Br− > Cl− ≫ ISE−) differed from the sequence derived from measurements of apical membrane resistance (NO 3 − ≈ Br− ≈ Cl− > SCN− > I− ≈ ISE−). Accordingly, the conductance was inhibited by SCN− and I− which, from the potential measurements, appeared to be more permeable than Cl−. This finding agrees with observations of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channel reported recently. However, none of the commonly used Cl− channel blockers, such as 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB), 4,4′-diisothiocyanatostilbene-2,2′-disulphonic acid (DIDS), anthracene-9-carboxylic acid (9-AC) and glibenclamide reduced this conductance in Necturus gallbladder. In contrast to the situation in most other epithelia, elevation of intracellular Ca2+ concentration ([Ca2+]i) by ionomycin stimulated only K+ conductance and not that of Cl− in the apical cell membrane. Chelation of intracellular Ca2+ did not prevent the stimulation of Cl− conductance by forskolin. This indicates that [Ca2+]i does not have even a permissive role in the cyclic adenosine monophosphate-(cAMP)-mediated stimulation process, as would have been expected if exocytosis was involved. Further evidence against the involvement of exocytosis in the stimulation process came from the observation that the stimulation was not associated with an increase in apical membrane capacitance and was not suppressed by disruption of the cytoskeleton by preincubation of the tissue with cytochalasin D. The data indicate that Necturus gallbladder epithelium contains homologues of the CFTR Cl− channel which reside permanently in the apical cell membrane and which can be stimulated by a cAMP-dependent phosphorylation process without involvement of cell Ca2+ or exocytosis.
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tight junction tightness of Necturus gall bladder epithelium is not regulated by camp or intracellular ca2 i microscopic and general electrophysiological observations
Pflügers Archiv: European Journal of Physiology, 1993Co-Authors: Gabor Kottra, Winfried Haase, Eberhard FrömterAbstract:Following the publications by Duffey et al. [Nature 294:451 (1981)] and Palant et al. [Am J Physiol 245:C203 (1983)] it is generally accepted that tightjunction tightness of Necturus gall bladder epithelium is up-regulated by cAMP-mediated and Ca2+-mediated stimulation. This conclusion was mainly based on observed increases in transepithelial resistance (Rt). However, since in leaky epithelia Rt cannot be simply equated with the tight junction resistance (Rj), but may include large contributions from the lateral space resistance (Rlis), we asked whether the observed increases in Rt resulted indeed from Rj or whether Rlis also increased. The experiments were performed on Necturus gall bladders using forskolin or the Ca2+ ionophore A23187 as stimulants. Forskolin (2 μmol/l) had a biphasic effect. In the first 5 min Rt decreased from 128±13 to 119±14 Ω cm2 (P<0.05, n=10) which probably reflects stimulation of an apical cell membrane Cl− conductance (see accompanying paper). Subsequently Rt increased in approximately 30 min to 184±20 Ω cm2 and then remained fairly constant. Simultaneously the lateral spaces collapsed. If the spaces were now transiently opened by passing mucosa-positive direct current across the epithelium, Rt fell transiently to 111±7 Ω cm2, but returned gradually to its elevated level when the spaces collapsed again. When the spaces were constantly dilated by a serosa-positive hydrostatic pressure of 1 cm H2O, forskolin neither affected the space width nor increased Rt, and current passage was virtually ineffective, although the cells depolarized in response to forskolin as usual. Similar observations were made with A23187 (10 μmol/l). It collapsed the spaces and increased Rt within 15 min from 145±Ω cm2 to 174±9 Ω cm2 and both changes completely reverted during passage of mucosa-positive direct current. Together with the impedance measurements reported in the accompanying publication, the data indicate that the increase in Rt following application of forskolin or Ca2+ ionophores primarily reflects a rise in Rlis and that the tight-junction tightness of Necturus gall bladder epithelium is regulated neither by cAMP nor by an ionophore-induced increase in intracellular Ca2+.
Virginie Vlaeminckguillem - One of the best experts on this subject based on the ideXlab platform.
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pedomorphosis revisited thyroid hormone receptors are functional in Necturus maculosus
Evolution & Development, 2006Co-Authors: Rachid Safi, Virginie Vlaeminckguillem, Martine Duterquecoquillaud, Marilyne Duffraisse, Alain Margotat, Erica J Crespi, Isabelle Seugnet, Michelina Plateroti, Robert J. DenverAbstract:: Heterochrony, a difference in developmental timing, is a central concept in modern evolutionary biology. An example is pedomorphosis, retention of juvenile characteristics in sexually mature adults, a phenomenon largely represented in salamanders. The mudpuppy (Necturus maculosus) is an obligate pedomorphic amphibian, never undergoing metamorphosis. Thyroid hormone induces tissue transformation in metamorphosing species and this action is mediated by nuclear thyroid hormone (TH) receptors (TRs). The absence of metamorphosis in Necturus has been attributed to a resistance to TH action as treatment with exogenous TH fails to induce transformation. The failure to metamorphose could be due to the lack of TR expression in target tissues, or to a loss of TR function. Toward understanding the molecular basis for the failure of Necturus tissues to respond to TH, and the ultimate cause for the expression of the obligate pedomorphic life history, we characterized the structure, function, and expression of TR genes in Necturus. Strikingly, we found that Necturus TRalpha and TRbeta genes encode fully functional TR proteins. These TRs bind both DNA and TH and can transactivate target genes in response to TH. Both TRalpha and TRbeta are expressed in various tissues. TH treatment in vivo induced expression in the gill of some but not all genes known to be activated by TH in anuran larvae, caused whole organism metabolic effects, but induced no external morphological changes in adults or larvae. Thus, Necturus possesses fully functional TRs and its tissues are not generally resistant to the actions of TH. Rather, the absence of metamorphosis may be due to the loss of TH-dependent control of key genes required for tissue transformation.
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pedomorphosis revisited thyroid hormone receptors are functional in Necturus maculosus
Evolution & Development, 2006Co-Authors: Rachid Safi, Virginie Vlaeminckguillem, Martine Duterquecoquillaud, Marilyne Duffraisse, Alain Margotat, Erica J Crespi, Isabelle Seugnet, Michelina Plateroti, Robert J. DenverAbstract:SUMMARY Heterochrony, a difference in developmental timing, is a central concept in modern evolutionary biology. An example is pedomorphosis, retention of juvenile characteristics in sexually mature adults, a phenomenon largely represented in salamanders. The mudpuppy (Necturus maculosus) is an obligate pedomorphic amphibian, never undergoing metamorphosis. Thyroid hormone induces tissue transformation in metamorphosing species and this action is mediated by nuclear thyroid hormone (TH) receptors (TRs). The absence of metamorphosis in Necturus has been attributed to a resistance to TH action as treatment with exogenous TH fails to induce transformation. The failure to metamorphose could be due to the lack of TR expression in target tissues, or to a loss of TR function. Toward understanding the molecular basis for the failure of Necturus tissues to respond to TH, and the ultimate cause for the expression of the obligate pedomorphic life history, we characterized the structure, function, and expression of TR genes in Necturus. Strikingly, we found that Necturus TRα and TRβ genes encode fully functional TR proteins. These TRs bind both DNA and TH and can transactivate target genes in response to TH. Both TRα and TRβ are expressed in various tissues. TH treatment in vivo induced expression in the gill of some but not all genes known to be activated by TH in anuran larvae, caused whole organism metabolic effects, but induced no external morphological changes in adults or larvae. Thus, Necturus possesses fully functional TRs and its tissues are not generally resistant to the actions of TH. Rather, the absence of metamorphosis may be due to the loss of TH-dependent control of key genes required for tissue transformation.
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thyroid hormone receptor expression in the obligatory paedomorphic salamander Necturus maculosus
The International Journal of Developmental Biology, 2006Co-Authors: Virginie Vlaeminckguillem, Rachid Safi, Emmanuelle Leteurtre, Martine Duterquecoquillaud, Philippe Guillem, Vincent LaudetAbstract:Amphibian metamorphosis is under the strict control of thyroid hormones (TH). These hormones induce metamorphosis by controlling gene expression through binding to thyroid hormone receptors (TRs). Necturus maculosus is considered to be an obligatory paedomorphic Amphibian since metamorphosis never occurs spontaneously and cannot be induced by pharmacological means. Since metamorphosis depends on the acquisition of response of tadpole tissues to thyroid hormone, we aimed to determine TR gene expression patterns in Necturus maculosus as well as the expression of two TH-related genes: Cytosolic Thyroid Hormone-Binding Protein (CTHBP)-M2-pyruvate kinase, a gene encoding a cytosolic TH binding protein and stromelysin 3, a direct TH target gene in Xenopus laevis. Tissue samples were obtained from specimens of Necturus maculosus. We performed in situ hybridization using non-cross-hybridizing RNA probes obtained from the cloned Necturus TRalpha and TRbeta genes. We found clear expression of Necturus TRalpha gene in several tissues including the central nervous system, epithelial cells of digestive and urinary organs, as well as myocardium and skeletal muscle. TRbeta was also expressed in the brain. In other tissues, hybridization signals were too low to draw reliable conclusions about their precise distribution. In addition, we observed that the expression of CTHBP and ST3 is largely distinct from that of TRs. The fact that we observed a clear expression of TRalpha and TRbeta which are evolutionary conserved, suggests that Necturus tissues express TRs. Our results thus indicate that, in contrast to previously held hypotheses, Necturus tissues are TH responsive.
Rachid Safi - One of the best experts on this subject based on the ideXlab platform.
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pedomorphosis revisited thyroid hormone receptors are functional in Necturus maculosus
Evolution & Development, 2006Co-Authors: Rachid Safi, Virginie Vlaeminckguillem, Martine Duterquecoquillaud, Marilyne Duffraisse, Alain Margotat, Erica J Crespi, Isabelle Seugnet, Michelina Plateroti, Robert J. DenverAbstract:: Heterochrony, a difference in developmental timing, is a central concept in modern evolutionary biology. An example is pedomorphosis, retention of juvenile characteristics in sexually mature adults, a phenomenon largely represented in salamanders. The mudpuppy (Necturus maculosus) is an obligate pedomorphic amphibian, never undergoing metamorphosis. Thyroid hormone induces tissue transformation in metamorphosing species and this action is mediated by nuclear thyroid hormone (TH) receptors (TRs). The absence of metamorphosis in Necturus has been attributed to a resistance to TH action as treatment with exogenous TH fails to induce transformation. The failure to metamorphose could be due to the lack of TR expression in target tissues, or to a loss of TR function. Toward understanding the molecular basis for the failure of Necturus tissues to respond to TH, and the ultimate cause for the expression of the obligate pedomorphic life history, we characterized the structure, function, and expression of TR genes in Necturus. Strikingly, we found that Necturus TRalpha and TRbeta genes encode fully functional TR proteins. These TRs bind both DNA and TH and can transactivate target genes in response to TH. Both TRalpha and TRbeta are expressed in various tissues. TH treatment in vivo induced expression in the gill of some but not all genes known to be activated by TH in anuran larvae, caused whole organism metabolic effects, but induced no external morphological changes in adults or larvae. Thus, Necturus possesses fully functional TRs and its tissues are not generally resistant to the actions of TH. Rather, the absence of metamorphosis may be due to the loss of TH-dependent control of key genes required for tissue transformation.
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pedomorphosis revisited thyroid hormone receptors are functional in Necturus maculosus
Evolution & Development, 2006Co-Authors: Rachid Safi, Virginie Vlaeminckguillem, Martine Duterquecoquillaud, Marilyne Duffraisse, Alain Margotat, Erica J Crespi, Isabelle Seugnet, Michelina Plateroti, Robert J. DenverAbstract:SUMMARY Heterochrony, a difference in developmental timing, is a central concept in modern evolutionary biology. An example is pedomorphosis, retention of juvenile characteristics in sexually mature adults, a phenomenon largely represented in salamanders. The mudpuppy (Necturus maculosus) is an obligate pedomorphic amphibian, never undergoing metamorphosis. Thyroid hormone induces tissue transformation in metamorphosing species and this action is mediated by nuclear thyroid hormone (TH) receptors (TRs). The absence of metamorphosis in Necturus has been attributed to a resistance to TH action as treatment with exogenous TH fails to induce transformation. The failure to metamorphose could be due to the lack of TR expression in target tissues, or to a loss of TR function. Toward understanding the molecular basis for the failure of Necturus tissues to respond to TH, and the ultimate cause for the expression of the obligate pedomorphic life history, we characterized the structure, function, and expression of TR genes in Necturus. Strikingly, we found that Necturus TRα and TRβ genes encode fully functional TR proteins. These TRs bind both DNA and TH and can transactivate target genes in response to TH. Both TRα and TRβ are expressed in various tissues. TH treatment in vivo induced expression in the gill of some but not all genes known to be activated by TH in anuran larvae, caused whole organism metabolic effects, but induced no external morphological changes in adults or larvae. Thus, Necturus possesses fully functional TRs and its tissues are not generally resistant to the actions of TH. Rather, the absence of metamorphosis may be due to the loss of TH-dependent control of key genes required for tissue transformation.
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thyroid hormone receptor expression in the obligatory paedomorphic salamander Necturus maculosus
The International Journal of Developmental Biology, 2006Co-Authors: Virginie Vlaeminckguillem, Rachid Safi, Emmanuelle Leteurtre, Martine Duterquecoquillaud, Philippe Guillem, Vincent LaudetAbstract:Amphibian metamorphosis is under the strict control of thyroid hormones (TH). These hormones induce metamorphosis by controlling gene expression through binding to thyroid hormone receptors (TRs). Necturus maculosus is considered to be an obligatory paedomorphic Amphibian since metamorphosis never occurs spontaneously and cannot be induced by pharmacological means. Since metamorphosis depends on the acquisition of response of tadpole tissues to thyroid hormone, we aimed to determine TR gene expression patterns in Necturus maculosus as well as the expression of two TH-related genes: Cytosolic Thyroid Hormone-Binding Protein (CTHBP)-M2-pyruvate kinase, a gene encoding a cytosolic TH binding protein and stromelysin 3, a direct TH target gene in Xenopus laevis. Tissue samples were obtained from specimens of Necturus maculosus. We performed in situ hybridization using non-cross-hybridizing RNA probes obtained from the cloned Necturus TRalpha and TRbeta genes. We found clear expression of Necturus TRalpha gene in several tissues including the central nervous system, epithelial cells of digestive and urinary organs, as well as myocardium and skeletal muscle. TRbeta was also expressed in the brain. In other tissues, hybridization signals were too low to draw reliable conclusions about their precise distribution. In addition, we observed that the expression of CTHBP and ST3 is largely distinct from that of TRs. The fact that we observed a clear expression of TRalpha and TRbeta which are evolutionary conserved, suggests that Necturus tissues express TRs. Our results thus indicate that, in contrast to previously held hypotheses, Necturus tissues are TH responsive.
Robert J. Denver - One of the best experts on this subject based on the ideXlab platform.
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pedomorphosis revisited thyroid hormone receptors are functional in Necturus maculosus
Evolution & Development, 2006Co-Authors: Rachid Safi, Virginie Vlaeminckguillem, Martine Duterquecoquillaud, Marilyne Duffraisse, Alain Margotat, Erica J Crespi, Isabelle Seugnet, Michelina Plateroti, Robert J. DenverAbstract:SUMMARY Heterochrony, a difference in developmental timing, is a central concept in modern evolutionary biology. An example is pedomorphosis, retention of juvenile characteristics in sexually mature adults, a phenomenon largely represented in salamanders. The mudpuppy (Necturus maculosus) is an obligate pedomorphic amphibian, never undergoing metamorphosis. Thyroid hormone induces tissue transformation in metamorphosing species and this action is mediated by nuclear thyroid hormone (TH) receptors (TRs). The absence of metamorphosis in Necturus has been attributed to a resistance to TH action as treatment with exogenous TH fails to induce transformation. The failure to metamorphose could be due to the lack of TR expression in target tissues, or to a loss of TR function. Toward understanding the molecular basis for the failure of Necturus tissues to respond to TH, and the ultimate cause for the expression of the obligate pedomorphic life history, we characterized the structure, function, and expression of TR genes in Necturus. Strikingly, we found that Necturus TRα and TRβ genes encode fully functional TR proteins. These TRs bind both DNA and TH and can transactivate target genes in response to TH. Both TRα and TRβ are expressed in various tissues. TH treatment in vivo induced expression in the gill of some but not all genes known to be activated by TH in anuran larvae, caused whole organism metabolic effects, but induced no external morphological changes in adults or larvae. Thus, Necturus possesses fully functional TRs and its tissues are not generally resistant to the actions of TH. Rather, the absence of metamorphosis may be due to the loss of TH-dependent control of key genes required for tissue transformation.
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pedomorphosis revisited thyroid hormone receptors are functional in Necturus maculosus
Evolution & Development, 2006Co-Authors: Rachid Safi, Virginie Vlaeminckguillem, Martine Duterquecoquillaud, Marilyne Duffraisse, Alain Margotat, Erica J Crespi, Isabelle Seugnet, Michelina Plateroti, Robert J. DenverAbstract:: Heterochrony, a difference in developmental timing, is a central concept in modern evolutionary biology. An example is pedomorphosis, retention of juvenile characteristics in sexually mature adults, a phenomenon largely represented in salamanders. The mudpuppy (Necturus maculosus) is an obligate pedomorphic amphibian, never undergoing metamorphosis. Thyroid hormone induces tissue transformation in metamorphosing species and this action is mediated by nuclear thyroid hormone (TH) receptors (TRs). The absence of metamorphosis in Necturus has been attributed to a resistance to TH action as treatment with exogenous TH fails to induce transformation. The failure to metamorphose could be due to the lack of TR expression in target tissues, or to a loss of TR function. Toward understanding the molecular basis for the failure of Necturus tissues to respond to TH, and the ultimate cause for the expression of the obligate pedomorphic life history, we characterized the structure, function, and expression of TR genes in Necturus. Strikingly, we found that Necturus TRalpha and TRbeta genes encode fully functional TR proteins. These TRs bind both DNA and TH and can transactivate target genes in response to TH. Both TRalpha and TRbeta are expressed in various tissues. TH treatment in vivo induced expression in the gill of some but not all genes known to be activated by TH in anuran larvae, caused whole organism metabolic effects, but induced no external morphological changes in adults or larvae. Thus, Necturus possesses fully functional TRs and its tissues are not generally resistant to the actions of TH. Rather, the absence of metamorphosis may be due to the loss of TH-dependent control of key genes required for tissue transformation.
