title: NOTCH, a new signaling pathway implicated in holoprosencephaly.
abstract: 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.
authors.affiliation: Institut de Génétique et Développement, CNRS UMR6061, Université de Rennes 1, IFR140 GFAS, Faculté de Médecine, Rennes, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Dupé
authors.forename: Lucie
authors.initials: L
authors.lastname: Rochard
authors.forename: Sandra
authors.initials: S
authors.lastname: Mercier
authors.forename: Yann
authors.initials: Y
authors.lastname: Le Pétillon
authors.forename: Isabelle
authors.initials: I
authors.lastname: Gicquel
authors.forename: Claude
authors.initials: C
authors.lastname: Bendavid
authors.forename: Georges
authors.initials: G
authors.lastname: Bourrouillou
authors.forename: Usha
authors.initials: U
authors.lastname: Kini
authors.forename: Christel
authors.initials: C
authors.lastname: Thauvin-Robinet
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Bohan
authors.forename: Sylvie
authors.initials: S
authors.lastname: Odent
authors.forename: Christèle
authors.initials: C
authors.lastname: Dubourg
authors.forename: Véronique
authors.initials: V
authors.lastname: David
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000734:Androstenediols; D000818:Animals; D001483:Base Sequence; D002642:Chick Embryo; D005260:Female; D016142:Holoprosencephaly / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D017384:Sequence Deletion; D015398:Signal Transduction
chemical_list: D000734:Androstenediols; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051880:Receptors, Notch; C064045:delta protein; C022775:delta (2,16)-5 alpha-androstadiene-3,17-diol-3,17-diacetate