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Gene Review

Robo1  -  roundabout homolog 1 (Drosophila)

Mus musculus

 
 
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Disease relevance of Robo1

 

High impact information on Robo1

  • Here, we show that these two types of information are functionally integrated; activation of the transmembrane receptor Roundabout (Robo) by its ligand, the secreted repulsive guidance cue Slit, inactivates N-cadherin-mediated adhesion [4].
  • We have proposed that DUTT1, nested within homozygously deleted regions at 3p12-13, is the tumor suppressor gene that deletion-mapping and tumor suppression assays indicate is located in proximal 3p [1].
  • Robo1 regulates the development of major axon tracts and interneuron migration in the forebrain [5].
  • Such phenotypes of corticothalamic targeting were not observed in Robo1 knockout mice but, instead, both corticothalamic and thalamocortical axons aberrantly arrived at their respective targets at least 1 day earlier than controls [5].
  • The DUTT1 gene is located on human chromosome 3, band p12, within a region of nested homozygous deletions in breast and lung tumors [2].
 

Biological context of Robo1

  • In search of novel molecules involved in tooth morphogenesis, we analyzed mRNA expression of Slit1, -2 and -3, earlier characterized as secreted signals needed for axonal pathfinding and their two receptors Robo1 and -2 (Roundabout1 and -2) in the developing mouse first molar [6].
  • First described as an axonal guidance cue through its repulsive effect on neurons expressing its receptor Roundabout (Robo), the Slit ligand has effects on cell migration, axon branching and elongation [7].
  • Here we show that alternative splicing of the Dutt1/Robo1 gene results in two mRNA transcripts with different signal peptides, which are differentially expressed throughout mouse embryogenesis [8].
  • LAGs have been shown previously to be synthesized preferentially by these cells in the uterus and are expressed at the cell surface, where they participate in cell adhesion processes (Dutt, A., Tang., J.-P., and Carson, D. D. (1987) Dev. Biol. 119, 27-37) [9].
  • The steroid hormone 17 beta-estradiol dramatically induces uterine N-linked glycoprotein assembly [Dutt, A., Tang, J.-P., Welply, J. K., & Carson, D. D. (1986) Endocrinology (Baltimore) 118, 661-673] [10].
 

Anatomical context of Robo1

  • Slit2 has been shown to bind Robo1, mediating both neuronal and axonal guidance in the developing central nervous system (CNS), (Brose et al., 1999; Hu, H., 1999. Chemorepulsion of neuronal migration by Slit2 in the developing mammalian forebrain. Neuron 23, 703-711) [11].
  • At the late bud stage, however, Robo1 transcripts were evident in the primary enamel knot, and at the cap stage a pronounced expression was noted in the middle of the tooth germ covering the primary enamel knot and dental papilla mesenchyme [6].
  • In the spinal cord Rig-1 shows overlapping but distinct pattern of expression with Robo1 and Robo2 [12].
  • A screen for candidate genes mediating this process identified Slit, a ligand for the Roundabout (Robo) receptor previously associated with guidance of axonal projections during central nervous system development [13].
  • As lung development progresses, Robo-1 and Robo-2 expression localizes to only the airway epithelium [7].
 

Regulatory relationships of Robo1

 

Other interactions of Robo1

  • Using in situ hybridization on metanephric explant cultures and urogenital tract sections, the expression patterns of Slit1, 2, 3 and Robo1 and 2 were investigated during murine metanephric development [11].
  • In contrast, expression of Slit2 and -3 as well Robo1, and -2 was largely restricted to mesenchymal tissue components of the tooth until the bell stage [6].
  • These findings resemble those from the Drosophila ventral nerve cord and indicate that in vertebrates a low level of Robo expression occurs in the initial crossing of the midline, while a high level of expression in the postcrossing fibers prevents recrossing [15].
 

Analytical, diagnostic and therapeutic context of Robo1

References

  1. 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]
  2. 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]
  3. Gene expression signatures identify novel regulatory pathways during murine lung development: implications for lung tumorigenesis. Bonner, A.E., Lemon, W.J., You, M. J. Med. Genet. (2003) [Pubmed]
  4. Activation of the repulsive receptor Roundabout inhibits N-cadherin-mediated cell adhesion. Rhee, J., Mahfooz, N.S., Arregui, C., Lilien, J., Balsamo, J., VanBerkum, M.F. Nat. Cell Biol. (2002) [Pubmed]
  5. Robo1 regulates the development of major axon tracts and interneuron migration in the forebrain. Andrews, W., Liapi, A., Plachez, C., Camurri, L., Zhang, J., Mori, S., Murakami, F., Parnavelas, J.G., Sundaresan, V., Richards, L.J. Development (2006) [Pubmed]
  6. Slit1 is specifically expressed in the primary and secondary enamel knots during molar tooth cusp formation. Løes, S., Luukko, K., Kvinnsland, I.H., Kettunen, P. Mech. Dev. (2001) [Pubmed]
  7. Slit and robo: expression patterns in lung development. Anselmo, M.A., Dalvin, S., Prodhan, P., Komatsuzaki, K., Aidlen, J.T., Schnitzer, J.J., Wu, J.Y., Kinane, T.B. Gene Expr. Patterns (2003) [Pubmed]
  8. Temporal and spatial expression of two isoforms of the Dutt1/Robo1 gene in mouse development. Clark, K., Hammond, E., Rabbitts, P. FEBS Lett. (2002) [Pubmed]
  9. Lactosaminoglycan assembly, cell surface expression, and release by mouse uterine epithelial cells. Dutt, A., Carson, D.D. J. Biol. Chem. (1990) [Pubmed]
  10. Estrogen influences dolichyl phosphate distribution among glycolipid pools in mouse uteri. Carson, D.D., Tang, J.P., Hu, G. Biochemistry (1987) [Pubmed]
  11. Expression of the vertebrate Slit gene family and their putative receptors, the Robo genes, in the developing murine kidney. Piper, M., Georgas, K., Yamada, T., Little, M. Mech. Dev. (2000) [Pubmed]
  12. Rig-1 a new member of Robo family genes exhibits distinct pattern of expression during mouse development. Camurri, L., Mambetisaeva, E., Sundaresan, V. Gene Expr. Patterns (2004) [Pubmed]
  13. Slit and robo expression in the developing mouse lung. Greenberg, J.M., Thompson, F.Y., Brooks, S.K., Shannon, J.M., Akeson, A.L. Dev. Dyn. (2004) [Pubmed]
  14. Robo4 is a vascular-specific receptor that inhibits endothelial migration. Park, K.W., Morrison, C.M., Sorensen, L.K., Jones, C.A., Rao, Y., Chien, C.B., Wu, J.Y., Urness, L.D., Li, D.Y. Dev. Biol. (2003) [Pubmed]
  15. Dynamic expression patterns of Robo (Robo1 and Robo2) in the developing murine central nervous system. Sundaresan, V., Mambetisaeva, E., Andrews, W., Annan, A., Knöll, B., Tear, G., Bannister, L. J. Comp. Neurol. (2004) [Pubmed]
 
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