title: The role of chordin/Bmp signals in mammalian pharyngeal development and DiGeorge syndrome.
abstract: The chordin/Bmp system provides one of the best examples of extracellular signaling regulation in animal development. We present the phenotype produced by the targeted inactivation of the chordin gene in mouse. Chordin homozygous mutant mice show, at low penetrance, early lethality and a ventralized gastrulation phenotype. The mutant embryos that survive die perinatally, displaying an extensive array of malformations that encompass most features of DiGeorge and Velo-Cardio-Facial syndromes in humans. Chordin secreted by the mesendoderm is required for the correct expression of Tbx1 and other transcription factors involved in the development of the pharyngeal region. The chordin mutation provides a mouse model for head and neck congenital malformations that frequently occur in humans and suggests that chordin/Bmp signaling may participate in their pathogenesis.
authors.affiliation: Howard Hughes Medical Institute and Department of Biological Chemistry, University of California, Los Angeles, CA 90095-1662, USA. bachiller@hnsurg.medsch.ucla.edu
authors.forename: Daniel
authors.initials: D
authors.lastname: Bachiller
authors.forename: John
authors.initials: J
authors.lastname: Klingensmith
authors.forename: Natalya
authors.initials: N
authors.lastname: Shneyder
authors.forename: Uyen
authors.initials: U
authors.lastname: Tran
authors.forename: Ryan
authors.initials: R
authors.lastname: Anderson
authors.forename: Janet
authors.initials: J
authors.lastname: Rossant
authors.forename: E M
authors.initials: EM
authors.lastname: De Robertis
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D001842:Bone and Bones / Q000196:embryology; D004062:DiGeorge Syndrome / Q000196:embryology*; D004627:Embryonic Induction; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors / Q000096:biosynthesis / Q000235:genetics; D005775:Gastrula / Q000502:physiology; D005804:Genes, Lethal; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D009154:Mutation; D010614:Pharynx / Q000196:embryology*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D020825:T-Box Domain Proteins / Q000096:biosynthesis / Q000235:genetics
chemical_list: D019485:Bone Morphogenetic Proteins; C496457:Fgf8 protein, mouse; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D020825:T-Box Domain Proteins; C491573:Tbx1 protein, mouse; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors; C054234:chordin