Mutations in a human ROBO gene disrupt hindbrain axon pathway crossing and morphogenesis.
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.
Jen
Joanna C
JC
Department of Neurology, University of California, Los Angeles, CA 90095, USA. jjen@ucla.edu
Chan
Wai-Man
WM
Bosley
Thomas M
TM
Wan
Jijun
J
Carr
Janai R
JR
Rüb
Udo
U
Shattuck
David
D
Salamon
Georges
G
Kudo
Lili C
LC
Ou
Jing
J
Lin
Doris D M
DD
Salih
Mustafa A M
MA
Kansu
Tülay
T
Al Dhalaan
Hesham
H
Al Zayed
Zayed
Z
MacDonald
David B
DB
Stigsby
Bent
B
Plaitakis
Andreas
A
Dretakis
Emmanuel K
EK
Gottlob
Irene
I
Pieh
Christina
C
Traboulsi
Elias I
EI
Wang
Qing
Q
Wang
Lejin
L
Andrews
Caroline
C
Yamada
Koki
K
Demer
Joseph L
JL
Karim
Shaheen
S
Alger
Jeffry R
JR
Geschwind
Daniel H
DH
Deller
Thomas
T
Sicotte
Nancy L
NL
Nelson
Stanley F
SF
Baloh
Robert W
RW
Engle
Elizabeth C
EC
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
D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C499630:ROBO3 protein, human; D000097905:Roundabout Proteins