Journal
SCIENCE
Volume 304, Issue 5676, Pages 1509-1513Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1096437
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Funding
- NEI NIH HHS [EY15298, EY13583, EY15311, R01 EY008313, R01 EY008313-14, R01 EY013583, R01 EY015298, R01 EY012498, EY12498] Funding Source: Medline
- NHLBI NIH HHS [R01 HL066251] Funding Source: Medline
- NICHD NIH HHS [P30 HD018655, P30 HD 18655] Funding Source: Medline
- NIDCD NIH HHS [DC00162, DC05524] Funding Source: Medline
- NIMH NIH HHS [MH60233] Funding Source: Medline
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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.
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