Mutations in a human ROBO gene disrupt hindbrain axon pathway crossing and morphogenesis.

TitleMutations in a human ROBO gene disrupt hindbrain axon pathway crossing and morphogenesis.
Publication TypeJournal Article
Year of Publication2004
AuthorsJen, JC, Chan W-M, Bosley TM, Wan J, Carr JR, Rüb U, Shattuck D, Salamon G, Kudo LC, Ou J, Lin DDM, Salih MAM, Kansu T, Al Dhalaan H, Al Zayed Z, MacDonald DB, Stigsby B, Plaitakis A, Dretakis EK, Gottlob I, Pieh C, Traboulsi EI, Wang Q, Wang L, Andrews C, Yamada K, Demer JL, Karim S, Alger JR, Geschwind DH, Deller T, Sicotte NL, Nelson SF, Baloh RW, Engle EC
JournalScience (New York, N.Y.)
Date Published2004 Jun 4
KeywordsAdult, Alternative Splicing, Amino Acid Motifs, Amino Acid Sequence, Axons, Evoked Potentials, Motor, Evoked Potentials, Somatosensory, Female, Functional Laterality, Genetic Linkage, Humans, In Situ Hybridization, Magnetic Resonance Imaging, Male, Medulla Oblongata, Microsatellite Repeats, Molecular Sequence Data, Morphogenesis, Mutation, Neural Pathways, Ophthalmoplegia, Pedigree, Protein Structure, Tertiary, Receptors, Immunologic, Reverse Transcriptase Polymerase Chain Reaction, Rhombencephalon, Scoliosis, Sequence Analysis, DNA, Syndrome

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.

Alternate JournalScience