Browsing by Author "Power, Deborah M."
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- Effects of estrogens and estrogenic disrupting compounds on fish mineralized tissuesPublication . Pinto, Patricia IS; Estevao, Maria D.; Power, Deborah M.Estrogens play well-recognized roles in reproduction across vertebrates, but also intervene in a wide range of other physiological processes, including mineral homeostasis. Classical actions are triggered when estrogens bind and activate intracellular estrogen receptors (ERs), regulating the transcription of responsive genes, but rapid non-genomic actions initiated by binding to plasma membrane receptors were recently described. A wide range of structurally diverse compounds from natural and anthropogenic sources have been shown to interact with and disrupt the normal functions of the estrogen system, and fish are particularly vulnerable to endocrine disruption, as these compounds are frequently discharged or run-off into waterways. The effect of estrogen disruptors in fish has mainly been assessed in relation to reproductive endpoints, and relatively little attention has been given to other disruptive actions. This review will overview the actions of estrogens in fish, including ER isoforms, their expression, structure and mechanisms of action. The estrogen functions will be considered in relation to mineral homeostasis and actions on mineralized tissues. The impact of estrogenic endocrine disrupting compounds on fish mineralized tissues will be reviewed, and the potential adverse outcomes of exposure to such compounds will be discussed. Current lacunae in knowledge are highlighted along with future research priorities.
- Endocrine regulation of carbonate precipitate formation in marine fish intestine by stanniocalcin and PTHrPPublication . Gregorio, Silvia F.; Carvalho, Edison S. M.; Campinho, Marco A.; Power, Deborah M.; Canario, Adelino V. M.; Fuentes, JuanIn marine fish, high epithelial bicarbonate secretion by the intestine generates luminal carbonate precipitates of divalent cations that play a key role in water and ion homeostasis. In vitro studies highlight the involvement of the calciotropic hormones PTHrP (parathyroid hormone-related protein) and stanniocalcin (STC) in the regulation of epithelial bicarbonate transport. The present study tested the hypothesis that calciotropic hormones have a regulatory role in carbonate precipitate formation in vivo. Sea bream (Sparus aurata) juveniles received single intraperitoneal injections of piscine PTHrP(1-34), the PTH/PTHrP receptor antagonist PTHrP(7-34) or purified sea bream STC, or were passively immunized with polyclonal rabbit antisera raised against sea bream STC (STC-Ab). Endocrine effects on the expression of the basolateral sodium bicarbonate cotransporter (Slc4a4.A), the apical anion exchangers Slc26a6.A and Slc26a3.B, and the V-type proton pump beta-subunit (Atp6v1b) in the anterior intestine were evaluated. In keeping with their calciotropic nature, the hypocalcaemic factors PTHrP(7-34) and STC upregulated gene expression of all transporters. In contrast, the hypercalcaemic factor PTHrP(1-34) and STC antibodies downregulated transporters involved in the bicarbonate secretion cascade. Changes in intestine luminal precipitate contents provoked by calcaemic endocrine factors validated these results: 24 h postinjection either PTHrP(1-34) or immunization with STC-Ab reduced the carbonate precipitate content in the sea bream intestine. In contrast, the PTH/PTHrP receptor antagonist PTHrP(7-34) increased not only the precipitated fraction but also the concentration of HCO3 equivalents in the intestinal fluid. These results confirm the hypothesis that calciotropic hormones have a regulatory role in carbonate precipitate formation in vivo in the intestine of marine fish. Furthermore, they illustrate for the first time in fish the counteracting effect of PTHrP and STC, and reveal an unexpected contribution of calcaemic factors to acid-base balance.
- European sea bass genome and its variation provide insights into adaptation to euryhalinity and speciationPublication . Tine, Mbaye; Kuhl, Heiner; Gagnaire, Pierre-Alexandre; Louro, Bruno; Desmarais, Erick; Martins, Rute S. T.; Hecht, Jochen; Knaust, Florian; Belkhir, Khalid; Klages, Sven; Dieterich, Roland; Stueber, Kurt; Piferrer, Francesc; Guinand, Bruno; Bierne, Nicolas; Volckaert, Filip A. M.; Bargelloni, Luca; Power, Deborah M.; Bonhomme, Francois; Canario, Adelino V. M.; Reinhardt, RichardThe European sea bass (Dicentrarchus labrax) is a temperate-zone euryhaline teleost of prime importance for aquaculture and fisheries. This species is subdivided into two naturally hybridizing lineages, one inhabiting the north-eastern Atlantic Ocean and the other the Mediterranean and Black seas. Here we provide a high-quality chromosome-scale assembly of its genome that shows a high degree of synteny with the more highly derived teleosts. We find expansions of gene families specifically associated with ion and water regulation, highlighting adaptation to variation in salinity. We further generate a genome-wide variation map through RAD-sequencing of Atlantic and Mediterranean populations. We show that variation in local recombination rates strongly influences the genomic landscape of diversity within and differentiation between lineages. Comparing predictions of alternative demographic models to the joint allele-frequency spectrum indicates that genomic islands of differentiation between sea bass lineages were generated by varying rates of introgression across the genome following a period of geographical isolation.
- Fish lysozyme gene family evolution and divergent function in early developmentPublication . Li, Lisen; Cardoso, João C. R.; Félix, Rute; Mateus, Ana Patricia; Canario, Adelino; Power, Deborah M.Lysozymes are an ancient group of antimicrobial enzymes of the innate immune system. Here we provide a comparative analysis of the evolution and function of lysozymes during early development in fish, the most speciose vertebrate group. In fishes, lineage and species-specific evolution of both C-type (chicken or conventional) and G-type (goose type) genes occurred. Phylogenetic analysis revealed that the teleost lysozyme G-type members group with the tetrapod homologues but the teleost C-type form three different clusters with the tetrapods. Most of the teleost C-type cluster with tetrapod Lyz but there are some that group with the mammalian Lyzl1/2 and LALBA. This suggests that early in gnathostome evolution these genes already existed and that lyzl1/2 and lalba genes are present in fish and tetrapods. Gene synteny analysis to confirm sequence orthologies failed to identify conserved genome regions between teleosts and other vertebrates lysozyme gene regions suggesting that in the ancestral bony fish genome lyz, lyzl1/2, lalba and lyg precursor genes were transposed to different chromosome regions. The homologue of the mammalian lactalbumin (LALBA) gene was identified for the first time in teleosts and was expressed in skin and during egg and larval development. Lysozyme activity was detected in teleost eggs and varied between species and in the gilthead sea bream lyg and lalba transcript abundance differed in eggs and larvae from different brood stock suggesting differences exist in maternal innate immune protection.
- Maternal thyroid hormones are essential for neural development in ZebrafishPublication . Campinho, Marco António; Saraiva, João; Florindo, Claudia; Power, Deborah M.Teleost eggs contain an abundant store of maternal thyroid hormones (THs), and early in zebrafish embryonic development, all the genes necessary for TH signaling are expressed. Nonetheless the function of THs in embryonic development remains elusive. To test the hypothesis that THs are fundamental for zebrafish embryonic development, an monocarboxilic transporter 8 (Mct8) knockdown strategy was deployed to prevent maternal TH uptake. Absence of maternal THs did not affect early specification of the neural epithelia but profoundly modified later dorsal specification of the brain and spinal cord as well as specific neuron differentiation. Maternal THs acted upstream of pax2a, pax7, and pax8 genes but downstream of shha and fgf8a signaling. The lack of inhibitory spinal cord interneurons and increased motoneurons in the mct8 morphants is consistent with their stiff axial body and impaired mobility. The mct8 mutations are associated with X-linked mental retardation in humans, and the cellular and molecular consequences of MCT8 knockdown during embryonic development in zebrafish provides new insight into the potential role of THs in this condition.
- Memorium - Professor Ian HendersonPublication . Power, Deborah M.; Dores, Robert M.; Sheridan, Mark; Balment, RichardWe regret to report the death of Professor Ian Henderson an internationally recognised scientist who contributed enormously to the field of comparative endocrinology. He made major scientific discoveries and was also a tremendous servant to the scientific community through his international collaborations, organisation of international conferences, and in more recent years as Co-editor in-Chief of the journal of General and Comparative Endocrinology. Professor Ian Henderson joined Aubrey Gorbman as an editor-in-chief of GCE in 1990 and retired from the journal in 2012. Over his 21 years as the EiC he worked alongside Frank Moore (editor-in-chief, 1992–2000), and Bob Dores (2000–2016). Ian Henderson steered the journal with a firm hand through the turbulent passage from the traditional typewritten manuscript and “snail mail” postal delivery to the electronic manuscript and then the on-line web platform – no mean feat! He worked diligently to raise the impact factor of the journal and his intellect, rigorous approach and tireless efforts have ensured that the journal remains a scientific reference in the field today.
- Metagenetic analysis of patterns of distribution and diversity of marine meiobenthic eukaryotesPublication . Fonseca, Vera G.; Carvalho, Gary R.; Nichols, Ben; Quince, Christopher; Johnson, Harriet F.; Neill, Simon P.; Lambshead, John D.; Thomas, W. Kelley; Power, Deborah M.; Creer, SimonAimMeiofaunal communities that inhabit the marine benthos offer unique opportunities to simultaneously study the macroecology of numerous phyla that exhibit different life-history strategies. Here, we ask: (1) if the macroecology of meiobenthic communities is explained mainly by dispersal constraints or by environmental conditions; and (2) if levels of meiofaunal diversity surpass existing estimates based on morphological taxonomy. LocationUK and mainland European coast. MethodsNext-generation sequencing techniques (NGS; Roche 454 FLX platform) using 18S nuclear small subunit ribosomal DNA (rDNA) gene. Pyrosequences were analysed using AmpliconNoise followed by chimera removal using Perseus. ResultsRarefaction curves revealed that sampling saturation was only reached at 15% of sites, highlighting that the bulk of meiofaunal diversity is yet to be discovered. Overall, 1353 OTUs were recovered and assigned to 23 different phyla. The majority of sampled sites had c. 60-70 unique operational taxonomic units (OTUs) per site, indicating high levels of beta diversity. The environmental parameters that best explained community structure were seawater temperature, geographical distance and sediment size, but most of the variability (R-2=70%-80%) remains unexplained. Main conclusionsHigh percentages of endemic OTUs suggest that meiobenthic community composition is partly niche-driven, as observed in larger organisms, but also shares macroecological features of microorganisms by showing high levels of cosmopolitanism (albeit on a much smaller scale). Meiobenthic communities exhibited patterns of isolation by distance as well as associations between niche, latitude and temperature, indicating that meiobenthic communities result from a combination of niche assembly and dispersal processes. Conversely, isolation-by-distance patterns were not identified in the featured protists, suggesting that animals and protists adhere to radically different macroecological processes, linked to life-history strategies.
- Persistence of the ABCC6 genes and the emergence of the bony skeleton in vertebratesPublication . Parreira, Bruna; Cardoso, João; Costa, Rita; Couto, Ana Rita; Bruges-Armas, Jacome; Power, Deborah M.The ATP-binding cassette transporter 6 (ABCC6) gene encodes a cellular transmembrane protein transporter (MRP6) that is involved in the regulation of tissue calcification in mammals. Mutations in ABCC6 are associated with human ectopic calcification disorders. To gain insight into its evolution and involvement in tissue calcification we conducted a comparative analysis of the ABCC6 gene and the related gene ABCC1 from invertebrates to vertebrates where a bony endoskeleton first evolved. Taking into consideration the role of ABCC6 in ectopic calcification of human skin we analysed the involvement of both genes in the regeneration of scales, mineralized structures that develop in fish skin. The ABCC6 gene was only found in bony vertebrate genomes and was absent from Elasmobranchs, Agnatha and from invertebrates. In teleost fish the abcc6 gene duplicated but the two genes persisted only in some teleost genomes. Six disease causing amino acid mutations in human MRP6 are a normal feature of abcc6 in fish, suggesting they do not have a deleterious effect on the protein. After scale removal the abcc6 (5 and 10 days) and abcc1 (10 days) gene expression was up-regulated relative to the intact control skin and this coincided with a time of intense scale mineralization.
- Phylogeny, expression patterns and regulation of DNA Methyltransferases in early development of the flatfish, Solea senegalensisPublication . Firmino, Joana; Carballo, Carlos; Armesto, Paula; Campinho, Marco António; Power, Deborah M.; Manchado, ManuelBackground: The identification of DNA methyltransferases (Dnmt) expression patterns during development and their regulation is important to understand the epigenetic mechanisms that modulate larval plasticity in marine fish. In this study, dnmt1 and dnmt3 paralogs were identified in the flatfish Solea senegalensis and expression patterns in early developmental stages and juveniles were determined. Additionally, the regulation of Dnmt transcription by a specific inhibitor (5-aza-2 '-deoxycytidine) and temperature was evaluated. Results: Five paralog genes of dnmt3, namely dnmt3aa, dnmt3ab, dnmt3ba, dnmt3bb. 1 and dnmt3bb. 2 and one gene for dnmt1 were identified. Phylogenetic analysis revealed that the dnmt gene family was highly conserved in teleosts and three fish-specific genes, dnmt3aa, dnmt3ba and dnmt3bb. 2 have evolved. The spatio-temporal expression patterns of four dnmts (dnmt1, dnmt3aa, dnmt3ab and dnmt3bb. 1) were different in early larval stages although all of them reduced expression with the age and were detected in neural organs and dnmt3aa appeared specific to somites. In juveniles, the four dnmt genes were expressed in brain and hematopoietic tissues such as kidney, spleen and gills. Treatment of sole embryos with 5-aza-2 '-deoxycytidine down-regulated dntm1 and up-regulated dntm3aa. Moreover, in lecithotrophic larval stages, dnmt3aa and dnmt3ab were temperature sensitive and their expression was higher in larvae incubated at 16 degrees C relative to 20 degrees C. Conclusion: Five dnmt3 and one dnmt1 paralog were identified in sole and their distinct developmental and tissue-specific expression patterns indicate that they may have different roles during development. The inhibitor 5-aza-2 '-deoxycytidine modified the transcript abundance of dntm1 and dntm3aa in embryos, which suggests that a regulatory feedback mechanism exists for these genes. The impact of thermal regime on expression levels of dnmt3aa and dnmt3ab in lecithotrophic larval stages suggests that these paralogs might be involved in thermal programing.
- Pth4, an ancient parathyroid hormone lost in eutherian mammals, reveals a new brain-to-bone signaling pathwayPublication . Suarez-Bregua, Paula; Torres-Nunez, Eva; Saxena, Ankur; Guerreiro, Pedro; Braasch, Ingo; Prober, David A.; Moran, Paloma; Miguel Cerda-Reverter, Jose; Du, Shao Jun; Adrio, Fatima; Power, Deborah M.; Canario, Adelino V. M.; Postlethwait, John H.; Bronner, Marianne E.; Canestro, Cristian; Rotllant, JosepRegulation of bone development, growth, and remodeling traditionally has been thought to depend on endocrine and autocrine/paracrine modulators. Recently, however, brain-derived signals have emerged as key regulators of bone metabolism, although their mechanisms of action have been poorly understood. We reveal the existence of an ancient parathyroid hormone (Pth)4 in zebrafish that was secondarily lost in the eutherian mammals' lineage, including humans, and that is specifically expressed in neurons of the hypothalamus and appears to be a central neural regulator of bone development and mineral homeostasis. Transgenic fish lines enabled mapping of axonal projections leading from the hypothalamus to the brainstem and spinal cord. Targeted laser ablation demonstrated an essential role for of pth4-expressing neurons in larval bone mineralization. Moreover, we show that Runx2 is a direct regulator of pth4 expression and that Pth4 can activate cAMP signaling mediated by Pth receptors. Finally, gain-of-function experiments show that Pth4 can alter calcium/phosphorus levels and affect expression of genes involved in phosphate homeostasis. Based on our discovery and characterization of Pth4, we propose a model for evolution of bone homeostasis in the context of the vertebrate transition from an aquatic to a terrestrial lifestyle.