Serotonin 2B receptor is required for heart development
| Autor: | Jean-Marie Launay, Pierre Hickel, Doo Sup Choi, Andrée Dierich, Marianne Le Meur, Canan G. Nebigil, Nadia Messaddeq, Luc Maroteaux |
|---|---|
| Přispěvatelé: | Laboratoire des biomolécules (LBM UMR 7203), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Chimie Moléculaire de Paris Centre (FR 2769), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Mayo Clinic [Rochester], Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut du Fer à Moulin (IFM - Inserm U1270 - SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Maroteaux, Luc, Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2000 |
| Předmět: |
MESH: Signal Transduction
Male MESH: Genes erbB-2 Receptor ErbB-2 MESH: Heterotrimeric GTP-Binding Proteins [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology MESH: Mice Knockout Receptor tyrosine kinase MESH: Animals Newborn Mice 0302 clinical medicine Receptor Serotonin 5-HT2B MESH: Animals Receptor Mice Knockout 0303 health sciences Multidisciplinary Heart development biology MESH: Kinetics Cell Differentiation Heart Biological Sciences Heterotrimeric GTP-Binding Proteins 5-HT2B receptor 3. Good health [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system MESH: Receptor ErbB-2 [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology Neuregulin MESH: Cell Division Female Signal transduction Cell Division Signal Transduction MESH: Cell Differentiation Heart Defects Congenital medicine.medical_specialty MESH: Receptors Serotonin MESH: Myocardium [SDV.GEN.GA] Life Sciences [q-bio]/Genetics/Animal genetics 03 medical and health sciences [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system Internal medicine Genetic model medicine Animals RNA Messenger MESH: Mice Fetal Death 030304 developmental biology Insulin-like growth factor 1 receptor MESH: RNA Messenger Myocardium MESH: Receptor Serotonin 5-HT2B MESH: Embryo Mammalian [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology MESH: Heart Defects Congenital Genes erbB-2 Embryo Mammalian MESH: Male MESH: Heart [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics Kinetics Endocrinology Animals Newborn MESH: Gene Deletion Receptors Serotonin biology.protein [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology MESH: Fetal Death MESH: Female 030217 neurology & neurosurgery Gene Deletion |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences, 2000, 97 (17), pp.9508-9513. ⟨10.1073/pnas.97.17.9508⟩ Proceedings of the National Academy of Sciences of the United States of America, 2000, 97 (17), pp.9508-9513. ⟨10.1073/pnas.97.17.9508⟩ |
| ISSN: | 0027-8424 1091-6490 |
| DOI: | 10.1073/pnas.97.17.9508⟩ |
| Popis: | Several lines of evidence suggest that the serotonin (5-hydroxytryptamine, 5-HT) regulates cardiovascular functions during embryogenesis and adulthood. 5-HT binds to numerous cognate receptors to initiate its biological effects. However, none of the 5-HT receptor disruptions in mice have yet resulted in embryonic defects. Here we show that 5-HT 2B receptor is an important regulator of cardiac development. We found that inactivation of 5-HT 2B gene leads to embryonic and neonatal death caused by heart defects. 5-HT 2B mutant embryos exhibit a lack of trabeculae in the heart and a specific reduction in the expression levels of a tyrosine kinase receptor, ErbB-2, leading to midgestation lethality. These in vivo data suggest that the Gq-coupled receptor 5-HT 2B uses the signaling pathway of tyrosine kinase receptor ErbB-2 for cardiac differentiation. All surviving newborn mice display a severe ventricular hypoplasia caused by impaired proliferative capacity of myocytes. In adult mutant mice, cardiac histopathological changes including myocyte disarray and ventricular dilation were consistently observed. Our results constitute genetic evidence that 5-HT via 5-HT 2B receptor regulates differentiation and proliferation of developing and adult heart. This mutation provides a genetic model for cardiopathy and should facilitate studies of both the pathogenesis and therapy of cardiac disorders in humans. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|