PUBLICATION
Mutations in a Human ROBO Gene Disrupt Hindbrain Axon Pathway Crossing and Morphogenesis
- Authors
- Jen, J.C., Chan, W.M., Bosley, T.M., Wan, J., Carr, J.R., Rub, U., Shattuck, D., Salamon, G., Kudo, L.C., Ou, J., Lin, D.D., Salih, M.A., Kansu, T., Al Dhalaan, H., Al Zayed, Z., MacDonald, D.B., Stigsby, B., Plaitakis, A., Dretakis, E.K., Gottlob, I., Pieh, C., Traboulsi, E.I., Wang, Q., Wang, L., Andrews, C., Yamada, K., Demer, J.L., Karim, S.S., Alger, J.R., Geschwind, D.H., Deller, T., Sicotte, N.L., Nelson, S.F., Baloh, R.W., and Engle, E.C.
- ID
- ZDB-PUB-040427-6
- Date
- 2004
- Source
- Science (New York, N.Y.) 304(5676): 1509-1513 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Adult
- Alternative Splicing
- Amino Acid Motifs
- Amino Acid Sequence
- Axons/physiology*
- Evoked Potentials, Motor
- Evoked Potentials, Somatosensory
- Female
- Functional Laterality
- Genetic Linkage
- Humans
- In Situ Hybridization
- Magnetic Resonance Imaging
- Male
- Medulla Oblongata/growth & development
- Medulla Oblongata/pathology
- Microsatellite Repeats
- Molecular Sequence Data
- Morphogenesis
- Mutation
- Neural Pathways
- Ophthalmoplegia/genetics*
- Ophthalmoplegia/pathology
- Ophthalmoplegia/physiopathology
- Pedigree
- Protein Structure, Tertiary
- Receptors, Immunologic/chemistry
- Receptors, Immunologic/genetics*
- Receptors, Immunologic/metabolism*
- Reverse Transcriptase Polymerase Chain Reaction
- Rhombencephalon/growth & development*
- Rhombencephalon/pathology
- Scoliosis/genetics*
- Scoliosis/pathology
- Scoliosis/physiopathology
- Sequence Analysis, DNA
- Syndrome
- PubMed
- 15105459 Full text @ Science
Citation
Jen, J.C., Chan, W.M., Bosley, T.M., Wan, J., Carr, J.R., Rub, U., Shattuck, D., Salamon, G., Kudo, L.C., Ou, J., Lin, D.D., Salih, M.A., Kansu, T., Al Dhalaan, H., Al Zayed, Z., MacDonald, D.B., Stigsby, B., Plaitakis, A., Dretakis, E.K., Gottlob, I., Pieh, C., Traboulsi, E.I., Wang, Q., Wang, L., Andrews, C., Yamada, K., Demer, J.L., Karim, S.S., Alger, J.R., Geschwind, D.H., Deller, T., Sicotte, N.L., Nelson, S.F., Baloh, R.W., and Engle, E.C. (2004) Mutations in a Human ROBO Gene Disrupt Hindbrain Axon Pathway Crossing and Morphogenesis. Science (New York, N.Y.). 304(5676):1509-1513.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping