Berenice Schaerlinger | Université de Lorraine (original) (raw)
Papers by Berenice Schaerlinger
Journal De La Societe De Biologie, 2004
EvoDevo, 2015
Background: Fish correspond to the most diversified phylum among vertebrates with a large variety... more Background: Fish correspond to the most diversified phylum among vertebrates with a large variety of species. Even if general features are distinguishable during the embryogenesis, several differences in term of timing, organ implementation or step progression always occur between species. Moreover, the developmental timing of wild nonmodel fish often presents variability within a species. In that context, it is necessary to define a model of developmental table flexible enough to describe fish development by integrating this variability and allow intra-and inter-specific comparisons. The elaboration of a model passes by the definition of new stages that could be easily observable on individuals. The present study aims at proposing such a model and describing accurately the Eurasian perch (Perca fluviatilis) embryogenesis using microscopic techniques among which time lapse video and histological studies. The Eurasian perch belongs to the Percidae family that includes 235 species classified in 11 genera. It is a member of the Perca gender and inhabits the Northern part of Europe and Asia. Results: At 13 °C, P. fluviatilis development elapses for 15 days from the fertilization to the first oral feeding. The staging division first took into account the cellular status to define periods, then the acquisition of new abilities by the embryo to further define stages. It allowed distinguishing two main stages during the cell cleavage period depending on the synchronization of the cell divisions, two stages during the gastrulation period depending on the cell speed migration and five stages during the organogenesis according to the acquisition of key abilities as proposed in the saltatory theory. During each stage, organs implementation was carefully followed with a particular attention for the visual and digestive systems. In addition, our study shows that embryos hatch at various developmental stages while they all begin to feed at a fixed date, 15 days after the fertilization whatever the spawn and the hatching date. These data give arguments to propose the first oral feeding as the best definition of the embryonic-to-larval transition. Conclusions: The present model of developmental table combines flexibility and accuracy allowing detailed description of non-model fish species and intra-and inter-specific comparisons.
British Journal of Pharmacology, 2003
1 The pharmaceutical compound, dihydroergotamine (DHE) is dispensed to prevent and reduce the occ... more 1 The pharmaceutical compound, dihydroergotamine (DHE) is dispensed to prevent and reduce the occurrence of migraine attacks. Although still controversial, the prophylactic effect of this drug is believed to be caused through blockade and/or activation of numerous receptors including serotonin (5-HT) receptors of the 5-HT 2 subtype. 2 To elucidate if 5-HT 2 receptors (5-HT 2 Rs) may be involved in DHE prophylactic effect, we performed investigations aimed to determine the respective pharmacological profile of DHE and of its major metabolite 8 0 -hydroxy-DHE (8 0 -OH-DHE) at the 5-HT 2B and 5-HT 2C Rs by binding, inositol triphosphate (IP 3 ) or cyclic GMP (cGMP) coupling studies in transfected fibroblasts. 3 DHE and 8 0 -OH-DHE are competitive compounds at 5-HT 2B and 5-HT 2C Rs. 8 0 -OH-DHE interaction at (5-HT 2B Rs) was best fitted by a biphasic competition curve and displayed the highest affinity with a K i of 5 nm. These two compounds acted as agonists for both receptors in respect to cGMP production with pEC 50 of 8.3270.09 for 8 0 -OH-DHE at 5-HT 2B and 7.8370.06 at 5-HT 2C Rs. 4 Knowing that the antimigraine prophylactic effect of DHE is only observed after long-term treatment, we chronically exposed the recombinant cells to DHE and 8 0 -OH-DHE. The number of 5-HT 2B R-binding sites was always more affected than 5-HT 2C Rs. At 5-HT 2B Rs, 8 0 -OH-DHE was more effective than DHE, with an uncoupling that persisted for more than 40 h for IP 3 or cGMP. By contrast, the 5-HT 2C R coupling was reversible after either treatment. 5 Chronic exposure to 8 0 -OH-DHE caused a persistent agonist-mediated desensitisation of 5-HT 2B , but not 5-HT 2C Rs. This may be of relevance to therapeutic actions of the compound.
Developmental Dynamics, 2007
Serotonin (5-HT) not only works as a neurotransmitter in the nervous system, but also as a morpho... more Serotonin (5-HT) not only works as a neurotransmitter in the nervous system, but also as a morphogenetic factor during early embryogenesis. In Drosophila, a previous report showed that embryos that lack the 5-HT 2Dro receptor locus, display abnormal gastrulation movements. In this work, we screened for point mutations in the 5-HT 2Dro receptor gene. We identified one point mutation that generates a gain of serotonin affinity for the receptor and affects germband extension: 5-HT 2Dro C1644 . Embryos homozygous for this point mutation display a fourfold increase in the maximal speed of ectodermal cell movements during the rapid phase of germband extension. Homozygous 5-HT 2Dro C1644 embryos present a cuticular phenotype, including a total lack of denticle belt. Identification of this gain of function mutation shows the participation of serotonin in the regulation of the cell speed movements during the germband extension and suggests a role of serotonin in the regulation of cuticular formation during early embryogenesis. Developmental Dynamics 236: 991-999, 2007.
Communications in agricultural and applied biological sciences
Journal de la Société de Biologie
In agreement with previous data in the literature, our results indicate that serotonin, a monoami... more In agreement with previous data in the literature, our results indicate that serotonin, a monoamine neurotransmitter, can also regulate cell proliferation, cell movements and cell differentiation. We have recently shown that serotonin is required for embryonic heart development. Genetic ablation of the 5-HT2B receptor leads to partial embryonic and postnatal lethality with abnormal heart development. Similar molecular mechanisms seem to be involved in adult cardiomyocytes since mutant mice surviving to adulthood display a dilated cardiomyopathy. Furthermore this receptor appears to be involved in survival of cardiomyocytes. The 5-HT2B receptor is also implicated in systemic hypertension. Furthermore, mice with pharmacological or genetic ablation of 5-HT2B receptor are totally resistant to hypoxia-induced pulmonary hypertension, indicating that this receptor is regulating the pathologic vascular proliferation leading to this disease. Underlying mechanisms are still to be discovered.
International Journal of …, 2001
Serotonin (5-hydroxytryptamine, 5-HT) binds to numerous cognate receptors to initiate its biologi... more Serotonin (5-hydroxytryptamine, 5-HT) binds to numerous cognate receptors to initiate its biological effects. In this review, we have focused on the 5-HT 2B receptor to address how signaling and expression of this receptor is specifically implicated in embryonic development and adult health and disease. Transduction of the 5-HT 2B signaling is complex, including phospholipase C and A 2 stimulation, cGMP production and a mitogenic signal that integrates the tyrosine kinase-signaling pathway. Furthermore, 5-HT, through the 5-HT 2B receptors, has the ability to control serotonergic differentiation of committed neuron-like cells. In addition, 5-HT 2B receptors are actively involved in the transient action of 5-HT during embryonic morphogenesis. Our recent data presented the first genetic evidence that 5-HT via 5-HT 2B receptors regulates cardiac embryonic development and adult functions and suggested that this receptor subtype may be involved in other physiopathological situations. In particular, 5-HT-dependent molecular mechanisms may be involved in embryonic development and postnatal maturation of the enteric nervous system. Also, the involvement of the 5-HT 2B receptor in the vascular growth often observed in hypertension is likely. These probably result from reactivation of developmentally regulated receptors in pathological situations. Finally, embryonic functions of 5-HT 2 receptors observed in Drosophila gastrulation suggest evolutionary conserved mechanisms.
Theriogenology, 2012
The success of reproduction depends greatly upon gamete quality, especially oocytes which carry m... more The success of reproduction depends greatly upon gamete quality, especially oocytes which carry most of the molecular material necessary for early embryogenesis. However, it remains difficult to find relevant morphologic and/or biochemical parameters to assess oocyte quality and thus have a reliable prediction of the reproduction performance. To understand which criteria are the most reliable to assess the reproductive success of the Eurasian perch (Perca fluviatilis), we measured 14 parameters characterizing female, spawn, oocyte, and embryonic or larval development on 20 independent spawn. A data analysis allowed the definition of two clusters of spawn with different larval characteristics: the first cluster was composed of spawn which led mainly to strong large larvae presenting a low deformity rate, while the second cluster rather corresponds to spawn leading to smaller and weaker larvae with a higher deformity rate. Moreover, a third cluster (unfertilized spawn) was studied. Our analysis revealed that most of the prefertilization biological traits that we studied appeared poorly relevant to predict larval features, proper embryonic development and deformity occurrences. We thus performed a large scale proteomic analysis to highlight proteins differently expressed in each spawn cluster. A 2D-DIGE study followed by an MS/MS spectrometry allowed the identification of 32 proteins involved in several biological functions and differently expressed between spawn clusters. Among them, proteins involved in cell response to the oxidative stress, as well as energetic metabolism, heat shock proteins and Vitellogenins are of particular interest. Several functions appear specific to a spawn cluster and could thus explain their corresponding reproduction performance. In the future, proteins involved in those cellular mechanisms may constitute molecular markers predictive of the reproduction performance in Perca fluviatilis.
The FASEB Journal, 2011
Somatic hypermutation diversifies antibody binding sites by introducing point mutations in the va... more Somatic hypermutation diversifies antibody binding sites by introducing point mutations in the variable domains of rearranged immunoglobulin genes. In this study, we analyzed somatic hypermutation in variable heavy-chain (VH) domains of specific IgM antibodies of the urodele amphibian Pleurodeles waltl, immunized either on Earth or onboard the Mir space station. To detect somatic hypermutation, we aligned the variable domains of IgM heavy-chain transcripts with the corresponding VH gene. We also quantified NF-κB and activation-induced cytidine deaminase transcripts. Results were compared with those obtained using control animals immunized on Earth. Our data show that, as in most species of ectotherms, somatic hypermutation in P. waltl exhibits a mutational bias toward G and C bases. Furthermore, we show for the first time that somatic hypermutation occurs in space following immunization but at a lower frequency. This decrease is not due to a decrease in food intake or of the B-cell receptor/antigen interaction or to the absence of the germinal center-associated nuclear protein. It likely results from the combination of several spaceflight-associated changes, such as the severe reduction in T-cell activation, important perturbations of the cytoskeleton, and changes in the distribution of lymphocyte subpopulations and adhesion molecule expression.
Developmental Dynamics, 2007
Serotonin (5-HT) not only works as a neurotransmitter in the nervous system, but also as a morpho... more Serotonin (5-HT) not only works as a neurotransmitter in the nervous system, but also as a morphogenetic factor during early embryogenesis. In Drosophila, a previous report showed that embryos that lack the 5-HT 2Dro receptor locus, display abnormal gastrulation movements. In this work, we screened for point mutations in the 5-HT 2Dro receptor gene. We identified one point mutation that generates a gain of serotonin affinity for the receptor and affects germband extension: 5-HT 2Dro C1644 . Embryos homozygous for this point mutation display a fourfold increase in the maximal speed of ectodermal cell movements during the rapid phase of germband extension. Homozygous 5-HT 2Dro C1644 embryos present a cuticular phenotype, including a total lack of denticle belt. Identification of this gain of function mutation shows the participation of serotonin in the regulation of the cell speed movements during the germband extension and suggests a role of serotonin in the regulation of cuticular formation during early embryogenesis. Developmental Dynamics 236: 991-999, 2007.
Molecular Immunology, 2008
Up to now, it was thought that urodele amphibians possessed only two IgH isotypes, IgM () and IgY... more Up to now, it was thought that urodele amphibians possessed only two IgH isotypes, IgM () and IgY (υ). By screening a Pleurodeles waltl Ig cDNA mini-library, we identified three isotypes: IgM, IgY and a previously unknown class. IgM are multimeric molecules and represent the most abundant isotype throughout the life of P. waltl. IgY are likely the counterpart of mammalian IgA. The new isotype has typical Ig H-chain characteristics and is expressed as both secretory and membrane forms. Our analyses indicate that this isotype is restricted to Pleurodeles. Consequently, we named it "IgP" () for Pleurodeles. This isotype is mainly expressed after hatching. Its expression decreases after metamorphosis. Our data indicate that IgP-expressing B cells present some similarities with mammalian B1-cells.
British Journal of Pharmacology, 2003
1 The pharmaceutical compound, dihydroergotamine (DHE) is dispensed to prevent and reduce the occ... more 1 The pharmaceutical compound, dihydroergotamine (DHE) is dispensed to prevent and reduce the occurrence of migraine attacks. Although still controversial, the prophylactic effect of this drug is believed to be caused through blockade and/or activation of numerous receptors including serotonin (5-HT) receptors of the 5-HT 2 subtype. 2 To elucidate if 5-HT 2 receptors (5-HT 2 Rs) may be involved in DHE prophylactic effect, we performed investigations aimed to determine the respective pharmacological profile of DHE and of its major metabolite 8 0 -hydroxy-DHE (8 0 -OH-DHE) at the 5-HT 2B and 5-HT 2C Rs by binding, inositol triphosphate (IP 3 ) or cyclic GMP (cGMP) coupling studies in transfected fibroblasts. 3 DHE and 8 0 -OH-DHE are competitive compounds at 5-HT 2B and 5-HT 2C Rs. 8 0 -OH-DHE interaction at (5-HT 2B Rs) was best fitted by a biphasic competition curve and displayed the highest affinity with a K i of 5 nm. These two compounds acted as agonists for both receptors in respect to cGMP production with pEC 50 of 8.3270.09 for 8 0 -OH-DHE at 5-HT 2B and 7.8370.06 at 5-HT 2C Rs. 4 Knowing that the antimigraine prophylactic effect of DHE is only observed after long-term treatment, we chronically exposed the recombinant cells to DHE and 8 0 -OH-DHE. The number of 5-HT 2B R-binding sites was always more affected than 5-HT 2C Rs. At 5-HT 2B Rs, 8 0 -OH-DHE was more effective than DHE, with an uncoupling that persisted for more than 40 h for IP 3 or cGMP. By contrast, the 5-HT 2C R coupling was reversible after either treatment. 5 Chronic exposure to 8 0 -OH-DHE caused a persistent agonist-mediated desensitisation of 5-HT 2B , but not 5-HT 2C Rs. This may be of relevance to therapeutic actions of the compound.
Developmental and Comparative Immunology, 2008
Until recently, it was believed that urodele amphibians are able to synthesize only two immunoglo... more Until recently, it was believed that urodele amphibians are able to synthesize only two immunoglobulin isotypes, IgM and IgY. We reinvestigated this issue in the Iberian ribbed newt Pleurodeles waltl and reported recently that this urodele expresses at least three isotypes: IgM, IgP and IgY. In this study, we demonstrate that another urodele, Ambystoma mexicanum, has also a third isotype whose amino acid sequence presents the highest homology with the amino acid sequence of Xenopus IgX. This isotype has typical Ig H-chain characteristics, could form multimers and is mainly expressed in mucosal tissues thereby indicating that it is likely the physiological counterpart of Xenopus IgX and mammalian IgA. Interestingly, no IgP could be found in A. mexicanum, in contrast to P. waltl, in which IgX was not found in previous investigations. These data indicate, for the first time, that different families of urodeles can express different immunoglobulin isotypes.
Journal De La Societe De Biologie, 2004
EvoDevo, 2015
Background: Fish correspond to the most diversified phylum among vertebrates with a large variety... more Background: Fish correspond to the most diversified phylum among vertebrates with a large variety of species. Even if general features are distinguishable during the embryogenesis, several differences in term of timing, organ implementation or step progression always occur between species. Moreover, the developmental timing of wild nonmodel fish often presents variability within a species. In that context, it is necessary to define a model of developmental table flexible enough to describe fish development by integrating this variability and allow intra-and inter-specific comparisons. The elaboration of a model passes by the definition of new stages that could be easily observable on individuals. The present study aims at proposing such a model and describing accurately the Eurasian perch (Perca fluviatilis) embryogenesis using microscopic techniques among which time lapse video and histological studies. The Eurasian perch belongs to the Percidae family that includes 235 species classified in 11 genera. It is a member of the Perca gender and inhabits the Northern part of Europe and Asia. Results: At 13 °C, P. fluviatilis development elapses for 15 days from the fertilization to the first oral feeding. The staging division first took into account the cellular status to define periods, then the acquisition of new abilities by the embryo to further define stages. It allowed distinguishing two main stages during the cell cleavage period depending on the synchronization of the cell divisions, two stages during the gastrulation period depending on the cell speed migration and five stages during the organogenesis according to the acquisition of key abilities as proposed in the saltatory theory. During each stage, organs implementation was carefully followed with a particular attention for the visual and digestive systems. In addition, our study shows that embryos hatch at various developmental stages while they all begin to feed at a fixed date, 15 days after the fertilization whatever the spawn and the hatching date. These data give arguments to propose the first oral feeding as the best definition of the embryonic-to-larval transition. Conclusions: The present model of developmental table combines flexibility and accuracy allowing detailed description of non-model fish species and intra-and inter-specific comparisons.
British Journal of Pharmacology, 2003
1 The pharmaceutical compound, dihydroergotamine (DHE) is dispensed to prevent and reduce the occ... more 1 The pharmaceutical compound, dihydroergotamine (DHE) is dispensed to prevent and reduce the occurrence of migraine attacks. Although still controversial, the prophylactic effect of this drug is believed to be caused through blockade and/or activation of numerous receptors including serotonin (5-HT) receptors of the 5-HT 2 subtype. 2 To elucidate if 5-HT 2 receptors (5-HT 2 Rs) may be involved in DHE prophylactic effect, we performed investigations aimed to determine the respective pharmacological profile of DHE and of its major metabolite 8 0 -hydroxy-DHE (8 0 -OH-DHE) at the 5-HT 2B and 5-HT 2C Rs by binding, inositol triphosphate (IP 3 ) or cyclic GMP (cGMP) coupling studies in transfected fibroblasts. 3 DHE and 8 0 -OH-DHE are competitive compounds at 5-HT 2B and 5-HT 2C Rs. 8 0 -OH-DHE interaction at (5-HT 2B Rs) was best fitted by a biphasic competition curve and displayed the highest affinity with a K i of 5 nm. These two compounds acted as agonists for both receptors in respect to cGMP production with pEC 50 of 8.3270.09 for 8 0 -OH-DHE at 5-HT 2B and 7.8370.06 at 5-HT 2C Rs. 4 Knowing that the antimigraine prophylactic effect of DHE is only observed after long-term treatment, we chronically exposed the recombinant cells to DHE and 8 0 -OH-DHE. The number of 5-HT 2B R-binding sites was always more affected than 5-HT 2C Rs. At 5-HT 2B Rs, 8 0 -OH-DHE was more effective than DHE, with an uncoupling that persisted for more than 40 h for IP 3 or cGMP. By contrast, the 5-HT 2C R coupling was reversible after either treatment. 5 Chronic exposure to 8 0 -OH-DHE caused a persistent agonist-mediated desensitisation of 5-HT 2B , but not 5-HT 2C Rs. This may be of relevance to therapeutic actions of the compound.
Developmental Dynamics, 2007
Serotonin (5-HT) not only works as a neurotransmitter in the nervous system, but also as a morpho... more Serotonin (5-HT) not only works as a neurotransmitter in the nervous system, but also as a morphogenetic factor during early embryogenesis. In Drosophila, a previous report showed that embryos that lack the 5-HT 2Dro receptor locus, display abnormal gastrulation movements. In this work, we screened for point mutations in the 5-HT 2Dro receptor gene. We identified one point mutation that generates a gain of serotonin affinity for the receptor and affects germband extension: 5-HT 2Dro C1644 . Embryos homozygous for this point mutation display a fourfold increase in the maximal speed of ectodermal cell movements during the rapid phase of germband extension. Homozygous 5-HT 2Dro C1644 embryos present a cuticular phenotype, including a total lack of denticle belt. Identification of this gain of function mutation shows the participation of serotonin in the regulation of the cell speed movements during the germband extension and suggests a role of serotonin in the regulation of cuticular formation during early embryogenesis. Developmental Dynamics 236: 991-999, 2007.
Communications in agricultural and applied biological sciences
Journal de la Société de Biologie
In agreement with previous data in the literature, our results indicate that serotonin, a monoami... more In agreement with previous data in the literature, our results indicate that serotonin, a monoamine neurotransmitter, can also regulate cell proliferation, cell movements and cell differentiation. We have recently shown that serotonin is required for embryonic heart development. Genetic ablation of the 5-HT2B receptor leads to partial embryonic and postnatal lethality with abnormal heart development. Similar molecular mechanisms seem to be involved in adult cardiomyocytes since mutant mice surviving to adulthood display a dilated cardiomyopathy. Furthermore this receptor appears to be involved in survival of cardiomyocytes. The 5-HT2B receptor is also implicated in systemic hypertension. Furthermore, mice with pharmacological or genetic ablation of 5-HT2B receptor are totally resistant to hypoxia-induced pulmonary hypertension, indicating that this receptor is regulating the pathologic vascular proliferation leading to this disease. Underlying mechanisms are still to be discovered.
International Journal of …, 2001
Serotonin (5-hydroxytryptamine, 5-HT) binds to numerous cognate receptors to initiate its biologi... more Serotonin (5-hydroxytryptamine, 5-HT) binds to numerous cognate receptors to initiate its biological effects. In this review, we have focused on the 5-HT 2B receptor to address how signaling and expression of this receptor is specifically implicated in embryonic development and adult health and disease. Transduction of the 5-HT 2B signaling is complex, including phospholipase C and A 2 stimulation, cGMP production and a mitogenic signal that integrates the tyrosine kinase-signaling pathway. Furthermore, 5-HT, through the 5-HT 2B receptors, has the ability to control serotonergic differentiation of committed neuron-like cells. In addition, 5-HT 2B receptors are actively involved in the transient action of 5-HT during embryonic morphogenesis. Our recent data presented the first genetic evidence that 5-HT via 5-HT 2B receptors regulates cardiac embryonic development and adult functions and suggested that this receptor subtype may be involved in other physiopathological situations. In particular, 5-HT-dependent molecular mechanisms may be involved in embryonic development and postnatal maturation of the enteric nervous system. Also, the involvement of the 5-HT 2B receptor in the vascular growth often observed in hypertension is likely. These probably result from reactivation of developmentally regulated receptors in pathological situations. Finally, embryonic functions of 5-HT 2 receptors observed in Drosophila gastrulation suggest evolutionary conserved mechanisms.
Theriogenology, 2012
The success of reproduction depends greatly upon gamete quality, especially oocytes which carry m... more The success of reproduction depends greatly upon gamete quality, especially oocytes which carry most of the molecular material necessary for early embryogenesis. However, it remains difficult to find relevant morphologic and/or biochemical parameters to assess oocyte quality and thus have a reliable prediction of the reproduction performance. To understand which criteria are the most reliable to assess the reproductive success of the Eurasian perch (Perca fluviatilis), we measured 14 parameters characterizing female, spawn, oocyte, and embryonic or larval development on 20 independent spawn. A data analysis allowed the definition of two clusters of spawn with different larval characteristics: the first cluster was composed of spawn which led mainly to strong large larvae presenting a low deformity rate, while the second cluster rather corresponds to spawn leading to smaller and weaker larvae with a higher deformity rate. Moreover, a third cluster (unfertilized spawn) was studied. Our analysis revealed that most of the prefertilization biological traits that we studied appeared poorly relevant to predict larval features, proper embryonic development and deformity occurrences. We thus performed a large scale proteomic analysis to highlight proteins differently expressed in each spawn cluster. A 2D-DIGE study followed by an MS/MS spectrometry allowed the identification of 32 proteins involved in several biological functions and differently expressed between spawn clusters. Among them, proteins involved in cell response to the oxidative stress, as well as energetic metabolism, heat shock proteins and Vitellogenins are of particular interest. Several functions appear specific to a spawn cluster and could thus explain their corresponding reproduction performance. In the future, proteins involved in those cellular mechanisms may constitute molecular markers predictive of the reproduction performance in Perca fluviatilis.
The FASEB Journal, 2011
Somatic hypermutation diversifies antibody binding sites by introducing point mutations in the va... more Somatic hypermutation diversifies antibody binding sites by introducing point mutations in the variable domains of rearranged immunoglobulin genes. In this study, we analyzed somatic hypermutation in variable heavy-chain (VH) domains of specific IgM antibodies of the urodele amphibian Pleurodeles waltl, immunized either on Earth or onboard the Mir space station. To detect somatic hypermutation, we aligned the variable domains of IgM heavy-chain transcripts with the corresponding VH gene. We also quantified NF-κB and activation-induced cytidine deaminase transcripts. Results were compared with those obtained using control animals immunized on Earth. Our data show that, as in most species of ectotherms, somatic hypermutation in P. waltl exhibits a mutational bias toward G and C bases. Furthermore, we show for the first time that somatic hypermutation occurs in space following immunization but at a lower frequency. This decrease is not due to a decrease in food intake or of the B-cell receptor/antigen interaction or to the absence of the germinal center-associated nuclear protein. It likely results from the combination of several spaceflight-associated changes, such as the severe reduction in T-cell activation, important perturbations of the cytoskeleton, and changes in the distribution of lymphocyte subpopulations and adhesion molecule expression.
Developmental Dynamics, 2007
Serotonin (5-HT) not only works as a neurotransmitter in the nervous system, but also as a morpho... more Serotonin (5-HT) not only works as a neurotransmitter in the nervous system, but also as a morphogenetic factor during early embryogenesis. In Drosophila, a previous report showed that embryos that lack the 5-HT 2Dro receptor locus, display abnormal gastrulation movements. In this work, we screened for point mutations in the 5-HT 2Dro receptor gene. We identified one point mutation that generates a gain of serotonin affinity for the receptor and affects germband extension: 5-HT 2Dro C1644 . Embryos homozygous for this point mutation display a fourfold increase in the maximal speed of ectodermal cell movements during the rapid phase of germband extension. Homozygous 5-HT 2Dro C1644 embryos present a cuticular phenotype, including a total lack of denticle belt. Identification of this gain of function mutation shows the participation of serotonin in the regulation of the cell speed movements during the germband extension and suggests a role of serotonin in the regulation of cuticular formation during early embryogenesis. Developmental Dynamics 236: 991-999, 2007.
Molecular Immunology, 2008
Up to now, it was thought that urodele amphibians possessed only two IgH isotypes, IgM () and IgY... more Up to now, it was thought that urodele amphibians possessed only two IgH isotypes, IgM () and IgY (υ). By screening a Pleurodeles waltl Ig cDNA mini-library, we identified three isotypes: IgM, IgY and a previously unknown class. IgM are multimeric molecules and represent the most abundant isotype throughout the life of P. waltl. IgY are likely the counterpart of mammalian IgA. The new isotype has typical Ig H-chain characteristics and is expressed as both secretory and membrane forms. Our analyses indicate that this isotype is restricted to Pleurodeles. Consequently, we named it "IgP" () for Pleurodeles. This isotype is mainly expressed after hatching. Its expression decreases after metamorphosis. Our data indicate that IgP-expressing B cells present some similarities with mammalian B1-cells.
British Journal of Pharmacology, 2003
1 The pharmaceutical compound, dihydroergotamine (DHE) is dispensed to prevent and reduce the occ... more 1 The pharmaceutical compound, dihydroergotamine (DHE) is dispensed to prevent and reduce the occurrence of migraine attacks. Although still controversial, the prophylactic effect of this drug is believed to be caused through blockade and/or activation of numerous receptors including serotonin (5-HT) receptors of the 5-HT 2 subtype. 2 To elucidate if 5-HT 2 receptors (5-HT 2 Rs) may be involved in DHE prophylactic effect, we performed investigations aimed to determine the respective pharmacological profile of DHE and of its major metabolite 8 0 -hydroxy-DHE (8 0 -OH-DHE) at the 5-HT 2B and 5-HT 2C Rs by binding, inositol triphosphate (IP 3 ) or cyclic GMP (cGMP) coupling studies in transfected fibroblasts. 3 DHE and 8 0 -OH-DHE are competitive compounds at 5-HT 2B and 5-HT 2C Rs. 8 0 -OH-DHE interaction at (5-HT 2B Rs) was best fitted by a biphasic competition curve and displayed the highest affinity with a K i of 5 nm. These two compounds acted as agonists for both receptors in respect to cGMP production with pEC 50 of 8.3270.09 for 8 0 -OH-DHE at 5-HT 2B and 7.8370.06 at 5-HT 2C Rs. 4 Knowing that the antimigraine prophylactic effect of DHE is only observed after long-term treatment, we chronically exposed the recombinant cells to DHE and 8 0 -OH-DHE. The number of 5-HT 2B R-binding sites was always more affected than 5-HT 2C Rs. At 5-HT 2B Rs, 8 0 -OH-DHE was more effective than DHE, with an uncoupling that persisted for more than 40 h for IP 3 or cGMP. By contrast, the 5-HT 2C R coupling was reversible after either treatment. 5 Chronic exposure to 8 0 -OH-DHE caused a persistent agonist-mediated desensitisation of 5-HT 2B , but not 5-HT 2C Rs. This may be of relevance to therapeutic actions of the compound.
Developmental and Comparative Immunology, 2008
Until recently, it was believed that urodele amphibians are able to synthesize only two immunoglo... more Until recently, it was believed that urodele amphibians are able to synthesize only two immunoglobulin isotypes, IgM and IgY. We reinvestigated this issue in the Iberian ribbed newt Pleurodeles waltl and reported recently that this urodele expresses at least three isotypes: IgM, IgP and IgY. In this study, we demonstrate that another urodele, Ambystoma mexicanum, has also a third isotype whose amino acid sequence presents the highest homology with the amino acid sequence of Xenopus IgX. This isotype has typical Ig H-chain characteristics, could form multimers and is mainly expressed in mucosal tissues thereby indicating that it is likely the physiological counterpart of Xenopus IgX and mammalian IgA. Interestingly, no IgP could be found in A. mexicanum, in contrast to P. waltl, in which IgX was not found in previous investigations. These data indicate, for the first time, that different families of urodeles can express different immunoglobulin isotypes.