Mutations in a Human ROBO Gene Disrupt Hindbrain Axon Pathway Crossing and Morphogenesis

Jen, Joanna C.; Chan, Wai-Man; Bosley, Thomas M.; Wan, Jijun; Carr, Janai R.; Rüb, Udo; Shattuck, David; Salamon, Georges; Kudo, Lili C.; Ou, Jing; Lin, Doris D. M.; Salih, Mustafa A. M.; Kansu, Tülay; al Dhalaan, Hesham; al Zayed, Zayed; MacDonald, David B.; Stigsby, Bent; Plaitakis, Andreas; Dretakis, Emmanuel K.; Gottlob, Irene; Pieh, Christina; Traboulsi, Elias I.; Wang, Qing; Wang, Lejin; Andrews, Caroline; Yamada, Koki; Demer, Joseph L.; Karim, Shaheen; Alger, Jeffry R.; Geschwind, Daniel H.; Deller, Thomas; Sicotte, Nancy L.; Nelson, Stanley F.; Baloh, Robert W.; Engle, Elizabeth C.

doi:10.1126/science.1096437

Cited by 386

The DOI matches its Crossref record; 19 of the 19 references it cites were found in a registry or an index.

Mutations in a Human ROBO Gene Disrupt Hindbrain Axon Pathway Crossing and Morphogenesis

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

DOI 10.1126/science.1096437

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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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19 of 19 references verified0 citation errors · 0 not checkable

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1 retracted

RETRACTED: Hierarchical Organization of Guidance Receptors: Silencing of Netrin Attraction by Slit Through a Robo/DCC Receptor Complex
Stein, E., & Tessier-Lavigne, M. (2001) · Science · doi:10.1126/science.1058445 · Cited by 601
Retracted
Slit Proteins Bind Robo Receptors and Have an Evolutionarily Conserved Role in Repulsive Axon Guidance
Brose, K., Bland, K. S., Wang, K. H., Arnott, D., Henzel, W., Goodman, C. S., Tessier-Lavigne, M., & Kidd, T. (1999) · Cell · doi:10.1016/s0092-8674(00)80590-5 · Cited by 1,223
Roundabout Controls Axon Crossing of the CNS Midline and Defines a Novel Subfamily of Evolutionarily Conserved Guidance Receptors
Kidd, T., Brose, K., Mitchell, K. J., Fetter, R. D., Tessier-Lavigne, M., Goodman, C. S., & Tear, G. (1998) · Cell · doi:10.1016/s0092-8674(00)80915-0 · Cited by 881
Mutations affecting growth cone guidance in drosophila: Genes necessary for guidance toward or away from the midline
Seeger, M., Tear, G., Ferres-Marco, D., & Goodman, C. S. (1993) · Neuron · doi:10.1016/0896-6273(93)90330-t · Cited by 683
Carpenter's Human Neuroanatomy
Parent, A., & Carpenter, M. B. (1996) · Medical Entomology and Zoology · Cited by 563
Directional guidance of neuronal migration in the olfactory system by the protein Slit
Wu, W., Wong, K., Chen, J.-H., Jiang, Z.-H., Dupuis, S., Wu, J. Y., & Rao, Y. (1999) · Nature · doi:10.1038/22477 · Cited by 528
The Divergent Robo Family Protein Rig-1/Robo3 Is a Negative Regulator of Slit Responsiveness Required for Midline Crossing by Commissural Axons
Sabatier, C., Plump, A. S., Ma, L., Brose, K., Tamada, A., Murakami, F., Lee, E. Y.-H. P., & Tessier-Lavigne, M. (2004) · Cell · doi:10.1016/s0092-8674(04)00303-4 · Cited by 430
Brain Stem Control of Spinal Mechanisms
Chandler, C., Hewitt, J. R., Miller, S. N., & Tan, N. (1982) · Cited by 428
Duane Radial Ray Syndrome (Okihiro Syndrome) Maps to 20q13 and Results from Mutations in SALL4, a New Member of the SAL Family
Al-Baradie, R., Yamada, K., St. Hilaire, C., Chan, W.-M., Andrews, C., McIntosh, N., Nakano, M., Martonyi, E. J., Raymond, W. R., Okumura, S., et al. (2002) · The American Journal of Human Genetics · doi:10.1086/343821 · Cited by 314
Self-citation
Selecting a Longitudinal Pathway
Rajagopalan, S., Vivancos, V., Nicolas, E., & Dickson, B. J. (2000) · Cell · doi:10.1016/s0092-8674(00)00207-5 · Cited by 278

Show all 19 references

Common mechanisms of nerve and blood vessel wiring
Carmeliet, P., & Tessier-Lavigne, M. (2005) · Nature · doi:10.1038/nature03875 · Cited by 1,085
Genome-wide association studies of brain imaging phenotypes in UK Biobank
Elliott, L. T., Sharp, K., Alfaro-Almagro, F., Shi, S., Miller, K. L., Douaud, G., Marchini, J., & Smith, S. M. (2018) · Nature · doi:10.1038/s41586-018-0571-7 · Cited by 834
Nephronophthisis-Associated Ciliopathies
Hildebrandt, F., & Zhou, W. (2007) · Journal of the American Society of Nephrology · doi:10.1681/asn.2006121344 · Cited by 406
The WAVE regulatory complex links diverse receptors to the actin cytoskeleton
Chen, B., Brinkmann, K., Chen, Z., Pak, C. W., Liao, Y., Shi, S., Henry, L., Grishin, N. V., Bogdan, S., & Rosen, M. K. (2014) · Cell · doi:10.1016/j.cell.2013.11.048 · Cited by 323
A developmental and genetic classification for midbrain-hindbrain malformations
Barkovich, A. J., Millen, K. J., & Dobyns, W. B. (2009) · Brain · doi:10.1093/brain/awp247 · Cited by 285

See all 386

Authors: Jen, J. C., Chan, W.-M., Bosley, T. M., Wan, J., Carr, J. R., Rüb, U., Shattuck, D., Salamon, G., Kudo, L. C., Ou, J., Lin, D. D. M., Salih, M. A. M., 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., Alger, J. R., Geschwind, D. H., Deller, T., Sicotte, N. L., Nelson, S. F., Baloh, R. W., & Engle, E. C.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2004-06-04
Volume: 304
Issue: 5676
Pages: 1509-1513
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.1096437
OpenAlex: W2116713316
Cited by: 386
References: 19
FWCI: 7.76
Type: journal article
Language: en
Open access: green

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This page: CoChat. (2026). Citation check: Mutations in a Human ROBO Gene Disrupt Hindbrain Axon Pathway Crossing and Morphogenesis. https://app.cochat.ai/papers/10.1126/science.1096437
The paper: Jen, J. C., Chan, W.-M., Bosley, T. M., Wan, J., Carr, J. R., Rüb, U., Shattuck, D., Salamon, G., Kudo, L. C., Ou, J., Lin, D. D. M., Salih, M. A. M., Kansu, T., al Dhalaan, H., al Zayed, Z., MacDonald, D. B., Stigsby, B., Plaitakis, A., Dretakis, E. K., . . . Engle, E. C. (2004). Mutations in a Human ROBO Gene Disrupt Hindbrain Axon Pathway Crossing and Morphogenesis. Science. https://doi.org/10.1126/science.1096437

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Mutations in a Human ROBO Gene Disrupt Hindbrain Axon Pathway Crossing and Morphogenesis

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