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John F. Mulley - One of the best experts on this subject based on the ideXlab platform.
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transcriptomic analysis of the lesser spotted catshark scyliorhinus canicula pancreas liver and brain reveals molecular level conservation of vertebrate pancreas function
BMC Genomics, 2014Co-Authors: John F. Mulley, Adam D Hargreaves, Matthew J Hegarty, Scott R Heller, Martin T SwainAbstract:Understanding the evolution of the vertebrate pancreas is key to understanding its functions. The chondrichthyes (Cartilaginous Fish such as sharks and rays) have often been suggested to possess the most ancient example of a distinct pancreas with both hormonal (endocrine) and digestive (exocrine) roles. The lack of genetic, genomic and transcriptomic data for Cartilaginous Fish has hindered a more thorough understanding of the molecular-level functions of the chondrichthyan pancreas, particularly with respect to their “unusual” energy metabolism (where ketone bodies and amino acids are the main oxidative fuel source) and their paradoxical ability to both maintain stable blood glucose levels and tolerate extensive periods of hypoglycemia. In order to shed light on some of these processes, we carried out the first large-scale comparative transcriptomic survey of multiple Cartilaginous Fish tissues: the pancreas, brain and liver of the lesser spotted catshark, Scyliorhinus canicula. We generated a mutli-tissue assembly comprising 86,006 contigs, of which 44,794 were assigned to a particular tissue or combination of tissues based on mapping of sequencing reads. We have characterised transcripts encoding genes involved in insulin regulation, glucose sensing, transcriptional regulation, signaling and digestion, as well as many peptide hormone precursors and their receptors for the first time. Comparisons to mammalian pancreas transcriptomes reveals that mechanisms of glucose sensing and insulin regulation used to establish and maintain a stable internal environment are conserved across jawed vertebrates and likely pre-date the vertebrate radiation. Conservation of pancreatic hormones and genes encoding digestive proteins support the single, early evolution of a distinct pancreatic gland with endocrine and exocrine functions in jawed vertebrates. In addition, we demonstrate that chondrichthyes lack pancreatic polypeptide (PP) and that reports of PP in the literature are likely due cross-reaction with PYY and/or NPY in the pancreas. A three hormone islet organ is therefore the ancestral jawed vertebrate condition, later elaborated upon only in the tetrapod lineage. The Cartilaginous Fish are a great untapped resource for the reconstruction of patterns and processes of vertebrate evolution and new approaches such as those described in this paper will greatly facilitate their incorporation into the rank of “model organism”.
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transcriptomic analysis of the lesser spotted catshark scyliorhinus canicula pancreas liver and brain reveals molecular level conservation of vertebrate pancreas function
bioRxiv, 2014Co-Authors: John F. Mulley, Adam D Hargreaves, Matthew J Hegarty, Scott R Heller, Martin T SwainAbstract:Background Understanding the evolution of the vertebrate pancreas is key to understanding its functions. The chondrichthyes (Cartilaginous Fish such as sharks and rays) have been suggested to possess the most ancient example of a distinct pancreas with both hormonal (endocrine) and digestive (exocrine) roles, although the lack of genetic, genomic and transcriptomic data for Cartilaginous Fish has hindered a more thorough understanding of the molecular-level functions of the chondrichthyan pancreas, particularly with respect to their unusual energy metabolism (where ketone bodies and amino acids are the main oxidative fuel source) and their paradoxical ability to both maintain stable blood glucose levels and tolerate extensive periods of hypoglycemia. In order to shed light on some of these processes we have carried out the first large-scale comparative transcriptomic survey of multiple Cartilaginous Fish tissues: the pancreas, brain and liver of the lesser spotted catshark, Scyliorhinus canicula. Results We generated a mutli-tissue assembly comprising 86,006 contigs, of which 44,794 were assigned to a particular tissue or combination of tissue based on mapping of sequencing reads. We have characterised transcripts encoding genes involved in insulin regulation, glucose sensing, transcriptional regulation, signaling and digestion, as well as many peptide hormone precursors and their receptors for the first time. Comparisons to published mammalian pancreas transcriptomes reveals that mechanisms of glucose sensing and insulin regulation used to establish and maintain a stable internal environment are conserved across jawed vertebrates and likely pre-date the vertebrate radiation. Conservation of pancreatic hormones and genes encoding digestive proteins support the single, early evolution of a distinct pancreatic gland with endocrine and exocrine functions in vertebrates, although the peptide diversity of the early vertebrate pancreas has been overestimated as a result of the use of cross-reacting antisera in earlier studies. A three hormone islet organ is therefore the basal vertebrate condition, later elaborated upon only in the tetrapod lineage. Conclusions The Cartilaginous Fish are a great untapped resource for the reconstruction of patterns and processes of vertebrate evolution and new approaches such as those described in this paper will greatly facilitate their incorporation into the rank of model organism.
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Parallel Retention of Pdx2 Genes in Cartilaginous Fish and Coelacanths
Molecular biology and evolution, 2010Co-Authors: John F. Mulley, Peter W. H. HollandAbstract:The Pdx1 or Ipf1 gene encodes an important homeodomain-containing protein with key roles in pancreas development and function. Mutations in human PDX1 are implicated in developmental defects and disease of the pancreas. Extensive research, including genome sequencing, has indicated that Pdx1 is the only member of its gene family in mammals, birds, amphibians, and ray-finned Fish, and with the exception of teleost Fish, this gene forms part of the ParaHox gene cluster along with Gsx1 and Cdx2. The ParaHox cluster, however, is a remnant of a 4-fold genome duplication; the three other ParaHox paralogues lack a Pdx-like gene in all vertebrate genomes examined to date. We have used bacterial artificial chromosome cloning and synteny analysis to show that the ancestor of living jawed vertebrates in fact had more ParaHox genes, including two Pdx genes (Pdx1 and Pdx2). Surprisingly, the two Pdx genes have been retained in parallel in two quite distantly related lineages, the Cartilaginous Fish (sharks, skates, and chimeras) and the Indonesian coelacanth, Latimeria menadoensis. The Pdx2 gene has been lost independently in ray-finned Fish and in tetrapods.
Martin T Swain - One of the best experts on this subject based on the ideXlab platform.
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transcriptomic analysis of the lesser spotted catshark scyliorhinus canicula pancreas liver and brain reveals molecular level conservation of vertebrate pancreas function
BMC Genomics, 2014Co-Authors: John F. Mulley, Adam D Hargreaves, Matthew J Hegarty, Scott R Heller, Martin T SwainAbstract:Understanding the evolution of the vertebrate pancreas is key to understanding its functions. The chondrichthyes (Cartilaginous Fish such as sharks and rays) have often been suggested to possess the most ancient example of a distinct pancreas with both hormonal (endocrine) and digestive (exocrine) roles. The lack of genetic, genomic and transcriptomic data for Cartilaginous Fish has hindered a more thorough understanding of the molecular-level functions of the chondrichthyan pancreas, particularly with respect to their “unusual” energy metabolism (where ketone bodies and amino acids are the main oxidative fuel source) and their paradoxical ability to both maintain stable blood glucose levels and tolerate extensive periods of hypoglycemia. In order to shed light on some of these processes, we carried out the first large-scale comparative transcriptomic survey of multiple Cartilaginous Fish tissues: the pancreas, brain and liver of the lesser spotted catshark, Scyliorhinus canicula. We generated a mutli-tissue assembly comprising 86,006 contigs, of which 44,794 were assigned to a particular tissue or combination of tissues based on mapping of sequencing reads. We have characterised transcripts encoding genes involved in insulin regulation, glucose sensing, transcriptional regulation, signaling and digestion, as well as many peptide hormone precursors and their receptors for the first time. Comparisons to mammalian pancreas transcriptomes reveals that mechanisms of glucose sensing and insulin regulation used to establish and maintain a stable internal environment are conserved across jawed vertebrates and likely pre-date the vertebrate radiation. Conservation of pancreatic hormones and genes encoding digestive proteins support the single, early evolution of a distinct pancreatic gland with endocrine and exocrine functions in jawed vertebrates. In addition, we demonstrate that chondrichthyes lack pancreatic polypeptide (PP) and that reports of PP in the literature are likely due cross-reaction with PYY and/or NPY in the pancreas. A three hormone islet organ is therefore the ancestral jawed vertebrate condition, later elaborated upon only in the tetrapod lineage. The Cartilaginous Fish are a great untapped resource for the reconstruction of patterns and processes of vertebrate evolution and new approaches such as those described in this paper will greatly facilitate their incorporation into the rank of “model organism”.
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transcriptomic analysis of the lesser spotted catshark scyliorhinus canicula pancreas liver and brain reveals molecular level conservation of vertebrate pancreas function
bioRxiv, 2014Co-Authors: John F. Mulley, Adam D Hargreaves, Matthew J Hegarty, Scott R Heller, Martin T SwainAbstract:Background Understanding the evolution of the vertebrate pancreas is key to understanding its functions. The chondrichthyes (Cartilaginous Fish such as sharks and rays) have been suggested to possess the most ancient example of a distinct pancreas with both hormonal (endocrine) and digestive (exocrine) roles, although the lack of genetic, genomic and transcriptomic data for Cartilaginous Fish has hindered a more thorough understanding of the molecular-level functions of the chondrichthyan pancreas, particularly with respect to their unusual energy metabolism (where ketone bodies and amino acids are the main oxidative fuel source) and their paradoxical ability to both maintain stable blood glucose levels and tolerate extensive periods of hypoglycemia. In order to shed light on some of these processes we have carried out the first large-scale comparative transcriptomic survey of multiple Cartilaginous Fish tissues: the pancreas, brain and liver of the lesser spotted catshark, Scyliorhinus canicula. Results We generated a mutli-tissue assembly comprising 86,006 contigs, of which 44,794 were assigned to a particular tissue or combination of tissue based on mapping of sequencing reads. We have characterised transcripts encoding genes involved in insulin regulation, glucose sensing, transcriptional regulation, signaling and digestion, as well as many peptide hormone precursors and their receptors for the first time. Comparisons to published mammalian pancreas transcriptomes reveals that mechanisms of glucose sensing and insulin regulation used to establish and maintain a stable internal environment are conserved across jawed vertebrates and likely pre-date the vertebrate radiation. Conservation of pancreatic hormones and genes encoding digestive proteins support the single, early evolution of a distinct pancreatic gland with endocrine and exocrine functions in vertebrates, although the peptide diversity of the early vertebrate pancreas has been overestimated as a result of the use of cross-reacting antisera in earlier studies. A three hormone islet organ is therefore the basal vertebrate condition, later elaborated upon only in the tetrapod lineage. Conclusions The Cartilaginous Fish are a great untapped resource for the reconstruction of patterns and processes of vertebrate evolution and new approaches such as those described in this paper will greatly facilitate their incorporation into the rank of model organism.
M.n. Dean - One of the best experts on this subject based on the ideXlab platform.
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Cartilaginous Fish Skeletal Anatomy ☆
Reference Module in Life Sciences, 2017Co-Authors: K.m. Claeson, M.n. DeanAbstract:Update of K.M. Claeson, M.N. Dean THE SKELETON | Cartilaginous Fish Skeletal Anatomy Encyclopedia of Fish Physiology, 2011, Pages 419-42
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Cartilaginous Fish skeletal tissues
2017Co-Authors: M.n. DeanAbstract:Most adult vertebrate animals have bony skeletons, with cartilage mostly restricted to joints and flexible structures. In contrast, the Chondrichthyes (sharks, batoids, and chimaeras) have endoskeletons made entirely of cartilage. Moreover, in sharks and batoids, most of the skeletal cartilage is tessellated, covered with mineralized, subperichondral blocks called tesserae. There are several other forms of cartilage found in the bodies of these Fishes that likely serve distinct functional and metabolic roles. The structure and development of chimaeroid cartilage is essentially unknown.
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Cartilaginous Fish skeletal anatomy
Encyclopedia of Fish Physiology, 2011Co-Authors: K.m. Claeson, M.n. DeanAbstract:Although the clades of Cartilaginous Fishes can be broadly considered to share a generalized skeletal bodyplan comprised of the same elements, their skeletons exhibit clade-specific arrangements and morphologies.
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the skeleton Cartilaginous Fish skeletal tissues
Encyclopedia of Fish Physiology#R##N#From Genome to Environment, 2011Co-Authors: M.n. DeanAbstract:Most adult vertebrate animals have bony skeletons, with cartilage mostly restricted to joints and flexible structures. In contrast, the Chondrichthyes (sharks, batoids, and chimaeras) have endoskeletons made entirely of cartilage. Moreover, in sharks and batoids, most of the skeletal cartilage is tessellated, covered with mineralized, subperichondral blocks called tesserae. There are several other forms of cartilage found in the bodies of these Fishes that likely serve distinct functional and metabolic roles. The structure and development of chimaeroid cartilage is essentially unknown.
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the skeleton Cartilaginous Fish skeletal anatomy
Encyclopedia of Fish Physiology#R##N#From Genome to Environment, 2011Co-Authors: K.m. Claeson, M.n. DeanAbstract:Although the clades of Cartilaginous Fishes can be broadly considered to share a generalized skeletal body plan comprised of the same elements, their skeletons exhibit clade-specific arrangements and morphologies.
Cheryll Tickle - One of the best experts on this subject based on the ideXlab platform.
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Fin development in a Cartilaginous Fish and the origin of vertebrate limbs
Nature, 2002Co-Authors: Mikiko Tanaka, W Gary Anderson, Neil Hazon, Andrea Münsterberg, Alan R. Prescott, Cheryll TickleAbstract:Recent fossil finds and experimental analysis of chick and mouse embryos highlighted the lateral fin fold theory, which suggests that two pairs of limbs in tetrapods evolved by subdivision of an elongated single fin. Here we examine fin development in embryos of the primitive Cartilaginous Fish, Scyliorhinus canicula (dogFish) using scanning electron microscopy and investigate expression of genes known to be involved in limb positioning, identity and patterning in higher vertebrates. Although we did not detect lateral fin folds in dogFish embryos, Engrailed-1 expression suggests that the body is compartmentalized dorso-ventrally. Furthermore, specification of limb identity occurs through the Tbx4 and Tbx5 genes, as in higher vertebrates. In contrast, unlike higher vertebrates, we did not detect Shh transcripts in dogFish fin-buds, although dHand (a gene involved in establishing Shh) is expressed. In S. canicula, the main fin axis seems to lie parallel to the body axis. 'Freeing' fins from the body axis and establishing a separate 'limb' axis has been proposed to be a crucial step in evolution of tetrapod limbs. We suggest that Shh plays a critical role in this process.
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P7 Fin development in a Cartilaginous Fish and the origin of vertebrate limbs.
Journal of anatomy, 2002Co-Authors: Mikiko Tanaka, Andrea Münsterberg, Wg Anderson, Ar Prescot, N Hazon, Cheryll TickleAbstract:Recent fossil finds and experimental analysis of chick and mouse embryos prompted us to re-explore the lateral fin fold theory which suggests that two pairs of limbs in tetrapods evolved by subdivision of an elongated single fin. We examined fin development in embryos of the primitive Cartilaginous Fish, Scyliorhinus canicula (dogFish) by scanning electron microscopy and investigated expression of genes known to be involved in limb positioning, identity and patterning in higher vertebrates. Although we did not detect lateral fin folds in dogFish embryos, Engrailed-1 expression suggests the body is compartmentalised dorsoventrally. Furthermore, specification of limb identity occurs via Tbx4 and Tbx5 genes as in higher vertebrates. In contrast, unlike higher vertebrates, we could not detect Shh transcripts in dogFish fin buds, although dHand (a gene involved in establishing Shh) is expressed. In S. canicula, the main fin axis seems to lie parallel to the body axis. Freeing fins from the body axis and establishing a separate limb axis has been proposed to be a crucial step in evolution of tetrapod limbs. We suggest that Shh plays a critical role in this process.
Byrappa Venkatesh - One of the best experts on this subject based on the ideXlab platform.
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transcriptional activation of a Cartilaginous Fish elephant shark callorhinchus milii mineralocorticoid receptor by corticosteroids progestins and spironolactone
bioRxiv, 2018Co-Authors: Yoshinao Katsu, Susumu Hyodo, Byrappa Venkatesh, Satomi Kohno, Kaori Oka, Xiaozhi Lin, Sumika Otake, Nisha E Pillai, Wataru Takagi, Michael E. BakerAbstract:A distinct mineralocorticoid receptor (MR) first appears in Cartilaginous Fishes (Chondrichthyes), the oldest group of extant jawed vertebrates. To investigate steroid specificity of Cartilaginous Fish MR, we studied transcriptional activation of full-length elephant shark (Callorhinchus milii) MR by aldosterone, cortisol, 11-deoxycorticosterone, corticosterone, 11-deoxcortisol, progesterone and 19-norprogesterone. All investigated corticosteroids and progestins showed half-maximal responses (EC50s) below 1 nM for elephant shark MR, and hence are potential physiological mineralocorticoids. Progesterone and 19-norprogesterone are antagonists for human, Xenopus and alligator MRs, but agonists for ray-finned Fish and chicken MRs, indicating that MR activation by progestins is an ancestral response, conserved in ray-finned Fish, lost in Xenopus, alligator and human, and distinct from chicken MR activation, which arose independently. RNA-seq analysis finds strong MR expression in elephant shark ovary and testis, in which progesterone-activated MR may have novel functions.
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Data_Sheet_2_Characterization of Gonadotropin-Releasing Hormone (GnRH) Genes From Cartilaginous Fish: Evolutionary Perspectives.PDF
2018Co-Authors: Anne-laure Gaillard, Byrappa Venkatesh, Boon-hui Tay, Daniela Pérez I. Sirkin, Anne-gaëlle Lafont, Céline De Flori, Paula G. Vissio, Sylvie Mazan, Sylvie Dufour, Hervé TostivintAbstract:The neuropeptide gonadotropin-releasing hormone (GnRH) plays an important role in the control of reproductive functions. Vertebrates possess multiple GnRH forms that are classified into three main groups, namely GnRH1, GnRH2, and GnRH3. In order to gain more insights into the GnRH gene family in vertebrates, we sought to identify which paralogs of this family are present in Cartilaginous Fish. For this purpose, we searched the genomes and/or transcriptomes of three representative species of this group, the small-spotted catshark, Scyliorhinus canicula, the whale shark, Rhincodon typus and the elephant shark Callorhinchus milii. In each species, we report the identification of three GnRH genes. In catshark and whale shark, phylogenetic and synteny analysis showed that these three genes correspond to GnRH1, GnRH2, and GnRH3. In both species, GnRH1 was found to encode a novel form of GnRH whose primary structure was determined as follows: QHWSFDLRPG. In elephant shark, the three genes correspond to GnRH1a and GnRH1b, two copies of the GnRH1 gene, plus GnRH2. 3D structure prediction of the chondrichthyan GnRH-associated peptides (GAPs) revealed that catshark GAP1, GAP2, and elephant shark GAP2 peptides exhibit a helix-loop-helix (HLH) structure. This structure observed for many osteichthyan GAP1 and GAP2, may convey GAP biological activity. This HLH structure could not be observed for elephant shark GAP1a and GAP1b. As for all other GAP3 described so far, no typical 3D HLH structure was observed for catshark nor whale shark GAP3. RT-PCR analysis revealed that GnRH1, GnRH2, and GnRH3 genes are differentially expressed in the catshark brain. GnRH1 mRNA appeared predominant in the diencephalon while GnRH2 and GnRH3 mRNAs seemed to be most abundant in the mesencephalon and telencephalon, respectively. Taken together, our results show that the GnRH gene repertoire of the vertebrate ancestor was entirely conserved in the chondrichthyan lineage but that the GnRH3 gene was probably lost in holocephali. They also suggest that the three GnRH neuronal systems previously described in the brain of bony vertebrates are also present in Cartilaginous Fish.
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Table_4_Characterization of Gonadotropin-Releasing Hormone (GnRH) Genes From Cartilaginous Fish: Evolutionary Perspectives.DOCX
2018Co-Authors: Anne-laure Gaillard, Byrappa Venkatesh, Boon-hui Tay, Daniela Pérez I. Sirkin, Anne-gaëlle Lafont, Céline De Flori, Paula G. Vissio, Sylvie Mazan, Sylvie Dufour, Hervé TostivintAbstract:The neuropeptide gonadotropin-releasing hormone (GnRH) plays an important role in the control of reproductive functions. Vertebrates possess multiple GnRH forms that are classified into three main groups, namely GnRH1, GnRH2, and GnRH3. In order to gain more insights into the GnRH gene family in vertebrates, we sought to identify which paralogs of this family are present in Cartilaginous Fish. For this purpose, we searched the genomes and/or transcriptomes of three representative species of this group, the small-spotted catshark, Scyliorhinus canicula, the whale shark, Rhincodon typus and the elephant shark Callorhinchus milii. In each species, we report the identification of three GnRH genes. In catshark and whale shark, phylogenetic and synteny analysis showed that these three genes correspond to GnRH1, GnRH2, and GnRH3. In both species, GnRH1 was found to encode a novel form of GnRH whose primary structure was determined as follows: QHWSFDLRPG. In elephant shark, the three genes correspond to GnRH1a and GnRH1b, two copies of the GnRH1 gene, plus GnRH2. 3D structure prediction of the chondrichthyan GnRH-associated peptides (GAPs) revealed that catshark GAP1, GAP2, and elephant shark GAP2 peptides exhibit a helix-loop-helix (HLH) structure. This structure observed for many osteichthyan GAP1 and GAP2, may convey GAP biological activity. This HLH structure could not be observed for elephant shark GAP1a and GAP1b. As for all other GAP3 described so far, no typical 3D HLH structure was observed for catshark nor whale shark GAP3. RT-PCR analysis revealed that GnRH1, GnRH2, and GnRH3 genes are differentially expressed in the catshark brain. GnRH1 mRNA appeared predominant in the diencephalon while GnRH2 and GnRH3 mRNAs seemed to be most abundant in the mesencephalon and telencephalon, respectively. Taken together, our results show that the GnRH gene repertoire of the vertebrate ancestor was entirely conserved in the chondrichthyan lineage but that the GnRH3 gene was probably lost in holocephali. They also suggest that the three GnRH neuronal systems previously described in the brain of bony vertebrates are also present in Cartilaginous Fish.
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Data_Sheet_7_Characterization of Gonadotropin-Releasing Hormone (GnRH) Genes From Cartilaginous Fish: Evolutionary Perspectives.DOCX
2018Co-Authors: Anne-laure Gaillard, Byrappa Venkatesh, Boon-hui Tay, Daniela Pérez I. Sirkin, Anne-gaëlle Lafont, Céline De Flori, Paula G. Vissio, Sylvie Mazan, Sylvie Dufour, Hervé TostivintAbstract:The neuropeptide gonadotropin-releasing hormone (GnRH) plays an important role in the control of reproductive functions. Vertebrates possess multiple GnRH forms that are classified into three main groups, namely GnRH1, GnRH2, and GnRH3. In order to gain more insights into the GnRH gene family in vertebrates, we sought to identify which paralogs of this family are present in Cartilaginous Fish. For this purpose, we searched the genomes and/or transcriptomes of three representative species of this group, the small-spotted catshark, Scyliorhinus canicula, the whale shark, Rhincodon typus and the elephant shark Callorhinchus milii. In each species, we report the identification of three GnRH genes. In catshark and whale shark, phylogenetic and synteny analysis showed that these three genes correspond to GnRH1, GnRH2, and GnRH3. In both species, GnRH1 was found to encode a novel form of GnRH whose primary structure was determined as follows: QHWSFDLRPG. In elephant shark, the three genes correspond to GnRH1a and GnRH1b, two copies of the GnRH1 gene, plus GnRH2. 3D structure prediction of the chondrichthyan GnRH-associated peptides (GAPs) revealed that catshark GAP1, GAP2, and elephant shark GAP2 peptides exhibit a helix-loop-helix (HLH) structure. This structure observed for many osteichthyan GAP1 and GAP2, may convey GAP biological activity. This HLH structure could not be observed for elephant shark GAP1a and GAP1b. As for all other GAP3 described so far, no typical 3D HLH structure was observed for catshark nor whale shark GAP3. RT-PCR analysis revealed that GnRH1, GnRH2, and GnRH3 genes are differentially expressed in the catshark brain. GnRH1 mRNA appeared predominant in the diencephalon while GnRH2 and GnRH3 mRNAs seemed to be most abundant in the mesencephalon and telencephalon, respectively. Taken together, our results show that the GnRH gene repertoire of the vertebrate ancestor was entirely conserved in the chondrichthyan lineage but that the GnRH3 gene was probably lost in holocephali. They also suggest that the three GnRH neuronal systems previously described in the brain of bony vertebrates are also present in Cartilaginous Fish.
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Characterization of Gonadotropin-Releasing Hormone (GnRH) Genes From Cartilaginous Fish: Evolutionary Perspectives
Frontiers in Neuroscience, 2018Co-Authors: Anne-laure Gaillard, Byrappa Venkatesh, Boon-hui Tay, Anne-gaëlle Lafont, Céline De Flori, Paula G. Vissio, Sylvie Mazan, Sylvie Dufour, Daniela Pérez Sirkin, Hervé TostivintAbstract:The neuropeptide gonadotropin-releasing hormone (GnRH) plays an important role in the control of reproductive functions. Vertebrates possess multiple GnRH forms that are classified into three main groups, namely GnRH1, GnRH2, and GnRH3. In order to gain more insights into the GnRH gene family in vertebrates, we sought to identify which paralogs of this family are present in Cartilaginous Fish. For this purpose, we searched the genomes and/or transcriptomes of three representative species of this group, the small-spotted catshark, Scyliorhinus canicula, the whale shark, Rhincodon typus and the elephant shark Callorhinchus milii. In each species, we report the identification of three GnRH genes. In catshark and whale shark, phylogenetic and synteny analysis showed that these three genes correspond to GnRH1, GnRH2, and GnRH3. In both species, GnRH1 was found to encode a novel form of GnRH whose primary structure was determined as follows: QHWSFDLRPG. In elephant shark, the three genes correspond to GnRH1a and GnRH1b, two copies of the GnRH1 gene, plus GnRH2. 3D structure prediction of the chondrichthyan GnRH-associated peptides (GAPs) revealed that catshark GAP1, GAP2, and elephant shark GAP2 peptides exhibit a helix-loop-helix (HLH) structure. This structure observed for many osteichthyan GAP1 and GAP2, may convey GAP biological activity. This HLH structure could not be observed for elephant shark GAP1a and GAP1b. As for all other GAP3 described so far, no typical 3D HLH structure was observed for catshark nor whale shark GAP3. RT-PCR analysis revealed that GnRH1, GnRH2, and GnRH3 genes are differentially expressed in the catshark brain. GnRH1 mRNA appeared predominant in the diencephalon while GnRH2 and GnRH3 mRNAs seemed to be most abundant in the mesencephalon and telencephalon, respectively. Taken together, our results show that the GnRH gene repertoire of the vertebrate ancestor was entirely conserved in the chondrichthyan lineage but that the GnRH3 gene was probably lost in holocephali. They also suggest that the three GnRH neuronal systems previously described in the brain of bony vertebrates are also present in Cartilaginous Fish.