2. Academic Validation
  3. Mutations in a human ROBO gene disrupt hindbrain axon pathway crossing and morphogenesis

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

  • Science. 2004 Jun 4;304(5676):1509-13. doi: 10.1126/science.1096437.
Joanna C Jen 1,  Wai-Man Chan,  Thomas M Bosley,  Jijun Wan,  Janai R Carr,  Udo Rüb,  David Shattuck,  Georges Salamon,  Lili C Kudo,  Jing Ou,  Doris D M Lin,  Mustafa A M Salih,  Tülay Kansu,  Hesham Al Dhalaan,  Zayed Al Zayed,  David B MacDonald,  Bent Stigsby,  Andreas Plaitakis,  Emmanuel K Dretakis,  Irene Gottlob,  Christina Pieh,  Elias I Traboulsi,  Qing Wang,  Lejin Wang,  Caroline Andrews,  Koki Yamada,  Joseph L Demer,  Shaheen Karim,  Jeffry R Alger,  Daniel H Geschwind,  Thomas Deller,  Nancy L Sicotte,  Stanley F Nelson,  Robert W Baloh,  Elizabeth C Engle
Affiliations

Affiliation

  • 1 Department of Neurology, University of California, Los Angeles, CA 90095, USA. jjen@ucla.edu
PMID: 15105459 DOI: 10.1126/science.1096437
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.

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