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Gene Review

sli  -  slit

Drosophila melanogaster

Synonyms: CG33464, CG43758, CG8355, CT21700, CT37068, ...
 
 
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High impact information on sli

  • Axon growth across the Drosophila midline requires Comm to downregulate Robo, the receptor for the midline repellent Slit [1].
  • slit: an EGF-homologous locus of D. melanogaster involved in the development of the embryonic central nervous system [2].
  • Neurobiology. Slit, the midline repellent [3].
  • We find identical axon guidance phenotypes in orbit/MAST and Abl mutants at the midline, where the repellent Slit restricts axon crossing [4].
  • We show that mediolateral position is determined in a binary fashion by expression (chordotonal neurons) or nonexpression (multidendritic neurons) of the Robo3 receptor for the midline repellent Slit [5].
 

Biological context of sli

  • Similarly, increasing the dosage of the two POU genes in sli mutant background enhances the penetrance of the RP2 lineage defects whereas reducing the dosage of the two genes reduces the penetrance of the phenotype [6].
  • Lateral positioning at the dorsal midline: Slit and Roundabout receptors guide Drosophila heart cell migration [7].
  • We examine the function of these proteins in the visual system by isolating a novel allele of slit that preferentially disrupts visual system expression of Slit and by creating transgenic RNA interference flies to inhibit the function of each Drosophila Robo in a tissue-specific fashion [8].
  • The development of Drosophila embryonic sense organs provides a neuronal migration paradigm where the in vivo roles of Slit and Robo can be assayed using genetics [9].
  • Binding site for Robo receptors revealed by dissection of the leucine-rich repeat region of Slit [10].
 

Anatomical context of sli

  • Repulsion is thought to be triggered by binding of the secreted protein Slit, which is expressed by midline glia, to Roundabout (Robo) receptors on growth cones [11].
  • We used molecular markers to characterize a boundary within the optic lobe of the Drosophila brain and found that Slit and the Robo family of receptors, well-known regulators of axon guidance and neuronal migration, inhibit the mixing of adjacent cell populations in the developing optic lobe [8].
  • RESULTS: Here we show that Slit-Robo signaling controls migration of Drosophila larval sensory neurons that are part of the Chordotonal (Cho) stretch receptor organs [9].
  • Robo2 overexpression in cis (in the sensory neurons) or in trans (on neighboring visceral mesoderm) transforms abdominal organs to a thoracic morphology and position by blocking migration, while loss of Slit-Robo signaling produces a reverse transformation in which thoracic organs migrate ectopically [9].
  • Attractive and repulsive functions of Slit are mediated by different receptors in the Drosophila trachea [12].
 

Associations of sli with chemical compounds

  • Biochemical studies suggest that guidance activity requires cell-surface heparan sulfate to promote binding of mammalian Slit/Robo homologs [13].
  • Our results are not consistent with the proposal based on genetic analysis in Drosophila that the sole function of Slit and Robo during midline guidance is to repress Netrin attraction [14].
  • Four sequence motifs comprise the structure of Slit: a leucine-rich repeat (LRR), epidermal growth factor-like (EGF) repeats, a laminin-like globular (G)-domain, and a cysteine domain [15].
 

Physical interactions of sli

  • We report here the isolation of vertebrate homologs of the Drosophila slit gene and show that Slit protein binds to the transmembrane protein Roundabout (Robo) [16].
 

Regulatory relationships of sli

  • Here we show that a combinatorial code of Robo receptors controls lateral position in the CNS by responding to this presumptive Slit gradient [17].
  • The Drosophila ARF6-GEF Schizo controls commissure formation by regulating Slit [18].
 

Other interactions of sli

  • Here, we report that the Drosophila homolog of Syndecan (reviewed in ), a heparan sulfate proteoglycan (HSPG), is required for proper Slit signaling [13].
  • In GMC-1 of the RP2/sib lineage, Slit promotes asymmetric division by down regulating two POU proteins, Nubbin and Mitimere [6].
  • Our data suggests that guidance of axons across brain hemispheres is mediated by Slit-dependent Robo2 signaling [19].
  • We find a robust and specific genetic interaction between capt and Abl at the midline choice point where the growth cone repellent Slit functions to restrict axon crossing [20].
  • Rhomboid 3 orchestrates Slit-independent repulsion of tracheal branches at the CNS midline [21].
 

Analytical, diagnostic and therapeutic context of sli

References

  1. Comm sorts robo to control axon guidance at the Drosophila midline. Keleman, K., Rajagopalan, S., Cleppien, D., Teis, D., Paiha, K., Huber, L.A., Technau, G.M., Dickson, B.J. Cell (2002) [Pubmed]
  2. slit: an EGF-homologous locus of D. melanogaster involved in the development of the embryonic central nervous system. Rothberg, J.M., Hartley, D.A., Walther, Z., Artavanis-Tsakonas, S. Cell (1988) [Pubmed]
  3. Neurobiology. Slit, the midline repellent. Harris, W.A., Holt, C.E. Nature (1999) [Pubmed]
  4. The microtubule plus end tracking protein Orbit/MAST/CLASP acts downstream of the tyrosine kinase Abl in mediating axon guidance. Lee, H., Engel, U., Rusch, J., Scherrer, S., Sheard, K., Van Vactor, D. Neuron (2004) [Pubmed]
  5. Genetic specification of axonal arbors: atonal regulates robo3 to position terminal branches in the Drosophila nervous system. Zlatic, M., Landgraf, M., Bate, M. Neuron (2003) [Pubmed]
  6. Slit signaling promotes the terminal asymmetric division of neural precursor cells in the Drosophila CNS. Mehta, B., Bhat, K.M. Development (2001) [Pubmed]
  7. Lateral positioning at the dorsal midline: Slit and Roundabout receptors guide Drosophila heart cell migration. Santiago-Martínez, E., Soplop, N.H., Kramer, S.G. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  8. Compartmentalization of visual centers in the Drosophila brain requires Slit and Robo proteins. Tayler, T.D., Robichaux, M.B., Garrity, P.A. Development (2004) [Pubmed]
  9. Roundabout 2 regulates migration of sensory neurons by signaling in trans. Kraut, R., Zinn, K. Curr. Biol. (2004) [Pubmed]
  10. Binding site for Robo receptors revealed by dissection of the leucine-rich repeat region of Slit. Howitt, J.A., Clout, N.J., Hohenester, E. EMBO J. (2004) [Pubmed]
  11. Receptor tyrosine phosphatases regulate axon guidance across the midline of the Drosophila embryo. Sun, Q., Bahri, S., Schmid, A., Chia, W., Zinn, K. Development (2000) [Pubmed]
  12. Attractive and repulsive functions of Slit are mediated by different receptors in the Drosophila trachea. Englund, C., Steneberg, P., Falileeva, L., Xylourgidis, N., Samakovlis, C. Development (2002) [Pubmed]
  13. Heparan sulfate proteoglycan syndecan promotes axonal and myotube guidance by slit/robo signaling. Steigemann, P., Molitor, A., Fellert, S., Jäckle, H., Vorbrüggen, G. Curr. Biol. (2004) [Pubmed]
  14. Independent functions of Slit-Robo repulsion and Netrin-Frazzled attraction regulate axon crossing at the midline in Drosophila. Garbe, D.S., Bashaw, G.J. J. Neurosci. (2007) [Pubmed]
  15. Repellent signaling by Slit requires the leucine-rich repeats. Battye, R., Stevens, A., Perry, R.L., Jacobs, J.R. J. Neurosci. (2001) [Pubmed]
  16. Vertebrate slit, a secreted ligand for the transmembrane protein roundabout, is a repellent for olfactory bulb axons. Li, H.S., Chen, J.H., Wu, W., Fagaly, T., Zhou, L., Yuan, W., Dupuis, S., Jiang, Z.H., Nash, W., Gick, C., Ornitz, D.M., Wu, J.Y., Rao, Y. Cell (1999) [Pubmed]
  17. Short-range and long-range guidance by Slit and its Robo receptors: a combinatorial code of Robo receptors controls lateral position. Simpson, J.H., Bland, K.S., Fetter, R.D., Goodman, C.S. Cell (2000) [Pubmed]
  18. The Drosophila ARF6-GEF Schizo controls commissure formation by regulating Slit. Onel, S., Bolke, L., Klämbt, C. Development (2004) [Pubmed]
  19. Positioning sensory terminals in the olfactory lobe of Drosophila by Robo signaling. Jhaveri, D., Saharan, S., Sen, A., Rodrigues, V. Development (2004) [Pubmed]
  20. A Drosophila homolog of cyclase-associated proteins collaborates with the Abl tyrosine kinase to control midline axon pathfinding. Wills, Z., Emerson, M., Rusch, J., Bikoff, J., Baum, B., Perrimon, N., Van Vactor, D. Neuron (2002) [Pubmed]
  21. Rhomboid 3 orchestrates Slit-independent repulsion of tracheal branches at the CNS midline. Gallio, M., Englund, C., Kylsten, P., Samakovlis, C. Development (2004) [Pubmed]
 
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