The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

ROBO1  -  roundabout, axon guidance receptor,...

Homo sapiens

Synonyms: DUTT1, Deleted in U twenty twenty, FLJ21882, H-Robo-1, Roundabout homolog 1, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of ROBO1

  • The mAb B2318C induced complement-dependent cytotoxicity in ROBO1-expressing cell lines and in the liver cancer cell line PLC/PRF/5 [1].
  • We demonstrate here that breast cancer cells and tissues derived from breast cancer patients express Robo 1 and 2 receptors [2].
  • Studies of the Slit-Robo complex may foster new anti-chemotactic approaches to block cancer cell metastasis [2].
  • We analysed DUTT1 for mutations in lung, breast and kidney cancers, no inactivating mutations were detected by PCR-SSCP [3].
  • Adjacent to one of these islands, we have identified and cloned a new gene (DUTT1) and used probes from this gene to detect two other homozygous deletions occurring in lung and breast carcinomas: the smallest deletion is within the gene itself and would result in a truncated protein [4].

Psychiatry related information on ROBO1


High impact information on ROBO1

  • The Slit protein guides neuronal and leukocyte migration through the transmembrane receptor Roundabout (Robo) [6].
  • Taking commissural axons in the vertebrate spinal cord and the Drosophila ventral nerve cord as examples, we examine how commissural axon pathfinding is regulated by the Slit family of guidance cues and their Robo family receptors [7].
  • Son of sevenless directly links the robo receptor to rac activation to control axon repulsion at the midline [8].
  • Here, the guidance ligand Slit and its receptor Robo control not whether axons cross (as in other midline decisions), but where the chiasm forms [9].
  • However, the molecular mechanisms by which Robo signaling leads to growth cone or neuron repulsion are still poorly understood [10].

Biological context of ROBO1

  • We recently demonstrated that ROBO1 is inactivated by promoter region hypermethylation in <20% of human cancers; furthermore, tumor suppressor activity has not been shown [11].
  • SLIT-ROBO signaling pathway is implicated in neurogenesis, angiogenesis, and immune response through the regulation of axonal guidance, endothelial cell migration, and denderitic cell migration, respectively [12].
  • We identified a high frequency of promoter hypermethylation in all the Slit-Robo genes resulting in down regulated gene expression in invasive CC, but the inhibitors of DNA methylation and histone deacetylases (HDACs) in CC cell lines failed to effectively reactivate the down-regulated expression [13].
  • These data suggest a wider range of functions for the Robo family in the development of the nervous system and provide novel insights into the molecular basis for the phenotypes observed in Robo mutants in Drosophila, C. elegans, and zebrafish [14].
  • It is therefore a candidate tumor suppressor gene in humans and is the homologue (ROBO1) of the Drosophila axonal guidance receptor gene, Roundabout [15].

Anatomical context of ROBO1

  • Expression of Robo receptor molecules is important for axon guidance across the midline of the mammalian central nervous system [16].
  • Slit, which mediates its function by binding to the Roundabout (Robo) receptor, has been shown to regulate neuronal and CXCR4-mediated leukocyte migration [2].
  • The Slit-Robo interactions mediate the repulsive cues on axons and growth cones during neural development [17].
  • Slit/Robo signaling is necessary to confine early neural crest cells to the ventral migratory pathway in the trunk [18].
  • A deleted form of the gene, which mimics a naturally occurring, tumor-associated human homozygous deletion of exon 2 of DUTT1/ROBO1, was introduced into the mouse germ line [19].

Associations of ROBO1 with chemical compounds

  • Heparin markedly enhances the affinity of the Slit-Robo interaction in a solid-phase binding assay [20].
  • The expression of DUTT1 gene was reactivated in HTB-19 after treatment with the demethylating agent 5-aza-2'-deoxycytidine [3].
  • Bisulfite sequencing of the promoter region of DUTT1 gene in the HTB-19 breast tumour cell line (not expressing DUTT1) showed complete hypermethylation of CpG sites within the promoter region of the DUTT1 gene (-244 to +27 relative to the translation start site) [3].
  • Here, we review the genetic and in vitro evidence implicating four families of ligand-receptor signalling systems common to both neuronal and vessel guidance: the Ephrins and Eph receptors; Semaphorins, Neuropilins and Plexin receptors; Netrin and Unc5 receptors; and Slits and Robo receptors [21].

Physical interactions of ROBO1

  • We demonstrate that the mouse SLIT1 protein can bind ROBO1, a transmembrane receptor implicated in axon guidance [22].

Regulatory relationships of ROBO1


Other interactions of ROBO1

  • SLIT2 protein is a putative ligand for the ROBO receptors [11].
  • Identification of ROBO1 as a novel hepatocellular carcinoma antigen and a potential therapeutic and diagnostic target [1].
  • The putative receptors for Slits, robo1 and robo2, are expressed in the inner retinal layer in which RGCs are located [24].
  • Robo1/Robo4: Differential expression of angiogenic markers in colorectal cancer [25].
  • Thus, our data suggest that a slight disturbance in neuronal axon crossing across the midline between brain hemispheres, dendrite guidance, or another function of ROBO1 may manifest as a specific reading disability in humans [5].

Analytical, diagnostic and therapeutic context of ROBO1

  • Analytical gel filtration chromatography demonstrates that Slit D2 associates with a soluble Robo fragment and a heparin-derived oligosaccharide to form a ternary complex [20].
  • DUTT1 expression was not detectable in one out of 18 breast tumour lines analysed by RT-PCR [3].
  • The overexpression of Robo1 and Robo4 in tumor vs. normal tissue was verified using real-time PCR [25].
  • By using overexpression studies and immunohistochemical and in situ hybridization techniques, we have investigated the role of Robo1 in the development of a subset of neurons and axon tracts in the Xenopus forebrain [26].
  • METHODS: Twenty-six normal corneas of 13 subjects and 41 penetrating keratoplasties (PKs) of 38 patients were photographed with a Keeler-Konan contact specular microscope and a Konan Noncon Robo automated noncontact specular microscope [27].


  1. Identification of ROBO1 as a novel hepatocellular carcinoma antigen and a potential therapeutic and diagnostic target. Ito, H., Funahashi, S., Yamauchi, N., Shibahara, J., Midorikawa, Y., Kawai, S., Kinoshita, Y., Watanabe, A., Hippo, Y., Ohtomo, T., Iwanari, H., Nakajima, A., Makuuchi, M., Fukayama, M., Hirata, Y., Hamakubo, T., Kodama, T., Tsuchiya, M., Aburatani, H. Clin. Cancer Res. (2006) [Pubmed]
  2. Slit protein-mediated inhibition of CXCR4-induced chemotactic and chemoinvasive signaling pathways in breast cancer cells. Prasad, A., Fernandis, A.Z., Rao, Y., Ganju, R.K. J. Biol. Chem. (2004) [Pubmed]
  3. Tumour specific promoter region methylation of the human homologue of the Drosophila Roundabout gene DUTT1 (ROBO1) in human cancers. Dallol, A., Forgacs, E., Martinez, A., Sekido, Y., Walker, R., Kishida, T., Rabbitts, P., Maher, E.R., Minna, J.D., Latif, F. Oncogene (2002) [Pubmed]
  4. Homozygous deletions at 3p12 in breast and lung cancer. Sundaresan, V., Chung, G., Heppell-Parton, A., Xiong, J., Grundy, C., Roberts, I., James, L., Cahn, A., Bench, A., Douglas, J., Minna, J., Sekido, Y., Lerman, M., Latif, F., Bergh, J., Li, H., Lowe, N., Ogilvie, D., Rabbitts, P. Oncogene (1998) [Pubmed]
  5. The axon guidance receptor gene ROBO1 is a candidate gene for developmental dyslexia. Hannula-Jouppi, K., Kaminen-Ahola, N., Taipale, M., Eklund, R., Nopola-Hemmi, J., Kääriäinen, H., Kere, J. PLoS Genet. (2005) [Pubmed]
  6. Signal transduction in neuronal migration: roles of GTPase activating proteins and the small GTPase Cdc42 in the Slit-Robo pathway. Wong, K., Ren, X.R., Huang, Y.Z., Xie, Y., Liu, G., Saito, H., Tang, H., Wen, L., Brady-Kalnay, S.M., Mei, L., Wu, J.Y., Xiong, W.C., Rao, Y. Cell (2001) [Pubmed]
  7. Regulation of commissural axon pathfinding by slit and its robo receptors. Dickson, B.J., Gilestro, G.F. Annu. Rev. Cell Dev. Biol. (2006) [Pubmed]
  8. Son of sevenless directly links the robo receptor to rac activation to control axon repulsion at the midline. Yang, L., Bashaw, G.J. Neuron (2006) [Pubmed]
  9. Generating X: formation of the optic chiasm. Rasband, K., Hardy, M., Chien, C.B. Neuron (2003) [Pubmed]
  10. Downstream of guidance receptors: entering the baroque period of axon guidance signaling. Schmucker, D. Neuron (2003) [Pubmed]
  11. SLIT2, a human homologue of the Drosophila Slit2 gene, has tumor suppressor activity and is frequently inactivated in lung and breast cancers. Dallol, A., Da Silva, N.F., Viacava, P., Minna, J.D., Bieche, I., Maher, E.R., Latif, F. Cancer Res. (2002) [Pubmed]
  12. Comparative genomics on SLIT1, SLIT2, and SLIT3 orthologs. Katoh, Y., Katoh, M. Oncol. Rep. (2005) [Pubmed]
  13. Promoter hypermethylation-mediated inactivation of multiple Slit-Robo pathway genes in cervical cancer progression. Narayan, G., Goparaju, C., Arias-Pulido, H., Kaufmann, A.M., Schneider, A., Dürst, M., Mansukhani, M., Pothuri, B., Murty, V.V. Mol. Cancer (2006) [Pubmed]
  14. Robo1 and Robo2 are homophilic binding molecules that promote axonal growth. Hivert, B., Liu, Z., Chuang, C.Y., Doherty, P., Sundaresan, V. Mol. Cell. Neurosci. (2002) [Pubmed]
  15. Targeted disruption of the 3p12 gene, Dutt1/Robo1, predisposes mice to lung adenocarcinomas and lymphomas with methylation of the gene promoter. Xian, J., Aitchison, A., Bobrow, L., Corbett, G., Pannell, R., Rabbitts, T., Rabbitts, P. Cancer Res. (2004) [Pubmed]
  16. Isolation and differential expression of two isoforms of the ROBO2/Robo2 axon guidance receptor gene in humans and mice. Yue, Y., Grossmann, B., Galetzka, D., Zechner, U., Haaf, T. Genomics (2006) [Pubmed]
  17. Frequent epigenetic inactivation of the SLIT2 gene in gliomas. Dallol, A., Krex, D., Hesson, L., Eng, C., Maher, E.R., Latif, F. Oncogene (2003) [Pubmed]
  18. Slit/Robo signaling is necessary to confine early neural crest cells to the ventral migratory pathway in the trunk. Jia, L., Cheng, L., Raper, J. Dev. Biol. (2005) [Pubmed]
  19. Inadequate lung development and bronchial hyperplasia in mice with a targeted deletion in the Dutt1/Robo1 gene. Xian, J., Clark, K.J., Fordham, R., Pannell, R., Rabbitts, T.H., Rabbitts, P.H. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  20. A molecular mechanism for the heparan sulfate dependence of slit-robo signaling. Hussain, S.A., Piper, M., Fukuhara, N., Strochlic, L., Cho, G., Howitt, J.A., Ahmed, Y., Powell, A.K., Turnbull, J.E., Holt, C.E., Hohenester, E. J. Biol. Chem. (2006) [Pubmed]
  21. Neuronal clues to vascular guidance. Suchting, S., Bicknell, R., Eichmann, A. Exp. Cell Res. (2006) [Pubmed]
  22. The mouse SLIT family: secreted ligands for ROBO expressed in patterns that suggest a role in morphogenesis and axon guidance. Yuan, W., Zhou, L., Chen, J.H., Wu, J.Y., Rao, Y., Ornitz, D.M. Dev. Biol. (1999) [Pubmed]
  23. Inhibition of medulloblastoma cell invasion by Slit. Werbowetski-Ogilvie, T.E., Seyed Sadr, M., Jabado, N., Angers-Loustau, A., Agar, N.Y., Wu, J., Bjerkvig, R., Antel, J.P., Faury, D., Rao, Y., Del Maestro, R.F. Oncogene (2006) [Pubmed]
  24. Slit2 is a repellent for retinal ganglion cell axons. Niclou, S.P., Jia, L., Raper, J.A. J. Neurosci. (2000) [Pubmed]
  25. Robo1/Robo4: Differential expression of angiogenic markers in colorectal cancer. Gröne, J., Doebler, O., Loddenkemper, C., Hotz, B., Buhr, H.J., Bhargava, S. Oncol. Rep. (2006) [Pubmed]
  26. Expression and role of Roundabout-1 in embryonic Xenopus forebrain. Connor, R.M., Key, B. Dev. Dyn. (2002) [Pubmed]
  27. Comparison of recording systems and analysis methods in specular microscopy. Ohno, K., Nelson, L.R., McLaren, J.W., Hodge, D.O., Bourne, W.M. Cornea (1999) [Pubmed]
WikiGenes - Universities