title: Mutations in a human ROBO gene disrupt hindbrain axon pathway crossing and morphogenesis.
abstract: The mechanisms controlling axon guidance are of fundamental importance in understanding brain development. Growing corticospinal and somatosensory axons cross the midline in the medulla to reach their targets and thus form the basis of contralateral motor control and sensory input. The motor and sensory projections appeared uncrossed in patients with horizontal gaze palsy with progressive scoliosis (HGPPS). In patients affected with HGPPS, we identified mutations in the ROBO3 gene, which shares homology with roundabout genes important in axon guidance in developing Drosophila, zebrafish, and mouse. Like its murine homolog Rig1/Robo3, but unlike other Robo proteins, ROBO3 is required for hindbrain axon midline crossing.
authors.affiliation: Department of Neurology, University of California, Los Angeles, CA 90095, USA. jjen@ucla.edu
authors.forename: Joanna C
authors.initials: JC
authors.lastname: Jen
authors.forename: Wai-Man
authors.initials: WM
authors.lastname: Chan
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Bosley
authors.forename: Jijun
authors.initials: J
authors.lastname: Wan
authors.forename: Janai R
authors.initials: JR
authors.lastname: Carr
authors.forename: Udo
authors.initials: U
authors.lastname: Rüb
authors.forename: David
authors.initials: D
authors.lastname: Shattuck
authors.forename: Georges
authors.initials: G
authors.lastname: Salamon
authors.forename: Lili C
authors.initials: LC
authors.lastname: Kudo
authors.forename: Jing
authors.initials: J
authors.lastname: Ou
authors.forename: Doris D M
authors.initials: DD
authors.lastname: Lin
authors.forename: Mustafa A M
authors.initials: MA
authors.lastname: Salih
authors.forename: Tülay
authors.initials: T
authors.lastname: Kansu
authors.forename: Hesham
authors.initials: H
authors.lastname: Al Dhalaan
authors.forename: Zayed
authors.initials: Z
authors.lastname: Al Zayed
authors.forename: David B
authors.initials: DB
authors.lastname: MacDonald
authors.forename: Bent
authors.initials: B
authors.lastname: Stigsby
authors.forename: Andreas
authors.initials: A
authors.lastname: Plaitakis
authors.forename: Emmanuel K
authors.initials: EK
authors.lastname: Dretakis
authors.forename: Irene
authors.initials: I
authors.lastname: Gottlob
authors.forename: Christina
authors.initials: C
authors.lastname: Pieh
authors.forename: Elias I
authors.initials: EI
authors.lastname: Traboulsi
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.forename: Lejin
authors.initials: L
authors.lastname: Wang
authors.forename: Caroline
authors.initials: C
authors.lastname: Andrews
authors.forename: Koki
authors.initials: K
authors.lastname: Yamada
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Demer
authors.forename: Shaheen
authors.initials: S
authors.lastname: Karim
authors.forename: Jeffry R
authors.initials: JR
authors.lastname: Alger
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Geschwind
authors.forename: Thomas
authors.initials: T
authors.lastname: Deller
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Sicotte
authors.forename: Stanley F
authors.initials: SF
authors.lastname: Nelson
authors.forename: Robert W
authors.initials: RW
authors.lastname: Baloh
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Engle
mesh_terms: D000328:Adult; D017398:Alternative Splicing; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001369:Axons / Q000502:physiology*; D019054:Evoked Potentials, Motor; D005073:Evoked Potentials, Somatosensory; D005260:Female; D007839:Functional Laterality; D008040:Genetic Linkage; D006801:Humans; D017403:In Situ Hybridization; D008279:Magnetic Resonance Imaging; D008297:Male; D008526:Medulla Oblongata / Q000254:growth & development / Q000473:pathology; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D009024:Morphogenesis; D009154:Mutation; D009434:Neural Pathways; D009886:Ophthalmoplegia / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D010375:Pedigree; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012249:Rhombencephalon / Q000254:growth & development* / Q000473:pathology; D012600:Scoliosis / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D017422:Sequence Analysis, DNA; D013577:Syndrome; D000097905:Roundabout Proteins
chemical_list: D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C499630:ROBO3 protein, human; D000097905:Roundabout Proteins