1. NOTCH, a new signaling pathway implicated in holoprosencephaly
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Valérie Dupé, Véronique David, Isabelle Gicquel, Christèle Dubourg, Yann Le Pétillon, Claude Bendavid, Timothy P. Bohan, Sandra Mercier, Usha Kini, Georges Bourrouillou, Sylvie Odent, Christel Thauvin-Robinet, Lucie Rochard, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Génétique Moléculaire, Hôpital Pontchaillou, Service de génétique médicale, CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Department of Clinical Genetics [Churchill Hospital], Churchill Hospital Oxford Centre for Haematology, Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Baylor University-Baylor University, Service de génétique clinique, hôpital Sud, Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de génétique moléculaire et génomique médicale [CHU Rennes], CHU Pontchaillou [Rennes], Service Génétique Médicale [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de génétique clinique [Rennes], Université de Rennes (UR)-CHU Pontchaillou [Rennes]-hôpital Sud, and De Villemeur, Hervé
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Male ,MESH: Signal Transduction ,Candidate gene ,[SDV.GEN] Life Sciences [q-bio]/Genetics ,Chick Embryo ,MESH: Amino Acid Sequence ,MESH: Base Sequence ,Holoprosencephaly ,MESH: Animals ,[SDV.BDD]Life Sciences [q-bio]/Development Biology ,Genetics (clinical) ,Sequence Deletion ,Genetics ,0303 health sciences ,Receptors, Notch ,MESH: Androstenediols ,030305 genetics & heredity ,MESH: Infant, Newborn ,Intracellular Signaling Peptides and Proteins ,General Medicine ,MESH: Sequence Deletion ,MESH: Chick Embryo ,Cell biology ,embryonic structures ,Female ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,MESH: Membrane Proteins ,Signal transduction ,MESH: Holoprosencephaly ,Signal Transduction ,Adult ,musculoskeletal diseases ,Cell signaling ,congenital, hereditary, and neonatal diseases and abnormalities ,animal structures ,Molecular Sequence Data ,Notch signaling pathway ,MESH: Sequence Alignment ,Biology ,Article ,03 medical and health sciences ,FGF8 ,[SDV.BDD] Life Sciences [q-bio]/Development Biology ,Androstenediols ,medicine ,Animals ,Humans ,[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Amino Acid Sequence ,Molecular Biology ,030304 developmental biology ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,MESH: Molecular Sequence Data ,MESH: Humans ,Base Sequence ,Infant, Newborn ,Membrane Proteins ,MESH: Adult ,medicine.disease ,MESH: Male ,Forebrain ,Mutation testing ,MESH: Receptors, Notch ,Sequence Alignment ,MESH: Female - Abstract
International audience; Genetics of Holoprosencephaly (HPE), a congenital malformation of the developing human forebrain, is due to multiple genetic defects. Most genes that have been implicated in HPE belong to the sonic hedgehog signaling pathway. Here we describe a new candidate gene isolated from array comparative genomic hybridization redundant 6qter deletions, DELTA Like 1 (DLL1), which is a ligand of NOTCH. We show that DLL1 is co-expressed in the developing chick forebrain with Fgf8. By treating chick embryos with a pharmacological inhibitor, we demonstrate that DLL1 interacts with FGF signaling pathway. Moreover, a mutation analysis of DLL1 in HPE patients revealed a three-nucleotide deletion. These various findings implicate DLL1 in early patterning of the forebrain and identify NOTCH as a new signaling pathway involved in HPE.
- Published
- 2011
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