Slits and Their Receptors

  • Alain Chédotal
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 621)


Slit was identified in Drosophila embryo as a gene involved in the patterning of larval cuticle 1. It was later shown that Slit is synthesized in the fly central nervous system by midline glia cells 2, 3, 4, 5. Slit homologues have since been found in C. elegans 6 and many vertebrate species, from amphibians, 7 fishes, 8 birds 9, 10, 11 to mammals 7 12, 13, 14. A single slit was isolated in invertebrates, whereas there are three slit genes (slit1–slit3) in mammals, that have around 60% homology 12. All encodes large ECM glycoproteins of about 200 kDa 15, 16 (Fig. 1A), comprising, from their N terminus to their C terminus, a long stretch of four leucine rich repeats (LRR) connected by disulphide bonds, seven to nine EGF repeats, a domain, named ALPS (Agrin, Perlecan, Laminin, Slit) or laminin G-like module (see ref. 17), and a cystein knot (Fig. 1A). Alternative spliced transcripts have been reported for Drosophila Slit 2, human Slit2 and Slit3, 14 and Slit1 18, 19. Moreover, two Slit1 isoforms exist in zebrafish as a consequence of gene duplication 20. Last, in mammals, two Slit2 isoforms can be purified from brain extracts, a long 200 kDa one 15, 16 and a shorter 150 kDa form (Slit2-N) that was shown to result from the proteolytic processing of full-length Slit2 21. Human Slit1 and Slit3 and Drosophila Slit are also cleaved by an unknown protease in a large N-terminal fragment and a shorter C-terminal fragment, suggesting conserved mechanisms for Slit cleavage across species 12, 21, 22, 23.

Moreover, Slit fragments have different cell association characteristics in cell culture suggesting that they may also have different extents of diffusion, different binding properties, and, hence, different functional activities in vivo. This conclusion is supported by in vitro data showing that full-length Slit2 functions as an antagonist of Slit2-N in the DRG branching assay, and that Slit2-N, not full-length Slit2, causes collapse of OB growth cones 24. In addition, Slit1-N and full-length Slit1 can induce branching of cortical neurons (see below), but only full-length Slit1 repels cortical axons 23.

Structure-function analysis in vertebrates and Drosophila demonstrated that the LRRs of Slits are required and sufficient to mediate their repulsive activities in neurons 24, 25, 26. More recent detailed structure function analysis of the LRR domains of Drosophila Slit, 27 revealed that the active site of Slit (at least regarding its pro-angiogenic activity) is located on the second of the fourth LRR (LRR2), which is highly conserved between Slits. Slit can also dimerize through the LRR4 domain and the cystein knot 18. However, a Slit1 spliced-variant that lacks the cysteine knot and does not dimerize is still able to repel OB axons 18.


Axon Guidance Rostral Migratory Stream Commissural Axon Retinal Axon Slit Function 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Nusslein-Volhard C, Wiechaus E, Kluding H. Mutations affecting the pattern of the larval cuticle in Drosophila melanogaster. I. Zygotic loci on the second chromosome. Roux Arch Dev Biol 1984; 193:267–283.Google Scholar
  2. 2.
    Rothberg JM, Artavanis-Tsakonas S. Modularity of the Slit protein characterization of a conserved carboxy-terminal sequence in secreted proteins and a motif implicated in extracellular protein interactions. J Mol Biol 1992; 227:367–370.PubMedGoogle Scholar
  3. 3.
    Kidd T, Bland KS, Goodman CS. Slit is the midline repellent for the robo receptor in drosophila. Cell 1999; 96:785–794.PubMedGoogle Scholar
  4. 4.
    Rajagopalan S, Nicolas E, Vivancos V et al. Crossing the midline: Roles and regulation of robo receptors. Neuron 2000; 28:767–777.PubMedGoogle Scholar
  5. 5.
    Simpson JH, Kidd T, Bland KS et al. Short-range and long-range guidance by slit and its robo receptors: Robo and Robo2 play distinct roles in midline guidance. Neuron 2000; 28:753–766.PubMedGoogle Scholar
  6. 6.
    Hao JC, Yu TW, Fujisawa K et al. C. elegans Slit Acts in midline, dorsal-ventral, and anterior-posterior guidance via the SAX-3/Robo receptor. Neuron 2001; 32(1):25–38.PubMedGoogle Scholar
  7. 7.
    Li HS, Chen JH, Wu W et al. Vertebrate Slit, a secreted ligand for the transmembrane protein roudabout, is a repellent for olfactory bulb axons. Cell 1999; 96:807–818.PubMedGoogle Scholar
  8. 8.
    Yee KT, Simon HH, Tessier-Lavigne M et al. Extension of long leading processes and neuronal migration in the mammalian brain directed by the chemoattractant netrin-1. Neuron 1999; 24(3):607–622.PubMedGoogle Scholar
  9. 9.
    Vargesson N, Luria V, Messina I et al. Expression patterns of Slit and Robo family members during vertebrate limb development. Mech Dev 2001; 106(1–2):175–180.PubMedGoogle Scholar
  10. 10.
    Holmes G, Niswander L. Expression of slit-2 and slit-3 during chick development. Dev Dyn 2001; 222(2):301–307.PubMedGoogle Scholar
  11. 11.
    Gilthorpe JD, Papantoniou EK, Chedotal A et al. The migration of cerebellar rhombic lip derivatives. Development 2002; 129(20):4719–4728.PubMedGoogle Scholar
  12. 12.
    Brose K, Bland KS, Wang KH et al. Slit proteins bind Robo receptors and have an evolutionarily conserved role in repulsive axon guidance. Cell 1999; 96:795–806.PubMedGoogle Scholar
  13. 13.
    Holmes GP, Negus K, Burridge L et al. Distinct but overlapping expression patterns of two vertebrate slit homologs implies functional roles in CNS development and organogenesis. Mech Dev 1998; 79:57–72.PubMedGoogle Scholar
  14. 14.
    Itoh A, Miyabayashi T, Ohno M et al. Cloning and expressions of three mammalian homologues of Drosophila slit suggest possible roles for slit in the formation and maintenance of the nervous system. Mol Brain Res 1998; 62:175–186.PubMedGoogle Scholar
  15. 15.
    Hu H. Chemorepulsion of neuronal migration by slit2 in the developing mammalian forebrain. Neuron 1999; 23:703–711.PubMedGoogle Scholar
  16. 16.
    Niclou SP, Jia L, Raper JA. Slit2 is a repellent for retinal ganglion cell axons. J Neurosci 2000; 20(13):4962–4974.PubMedGoogle Scholar
  17. 17.
    Nguyen-Ba-Charvet KT, Chédotal A. Role of Slit proteins in the vertebrate brain. J Physiol Paris 2002; 96:91–98.PubMedGoogle Scholar
  18. 18.
    Tanno T, Takenaka S, Tsuyama S. Expression and function of Slit1{alpha}, a novel alternative splicing product for Slit1. J Biochem 2004; 136(5):575–581.PubMedGoogle Scholar
  19. 19.
    Little M, Rumballe B, Georgas K et al. Conserved modularity and potential for alternate splicing in mouse and human Slit genes. Int J Dev Biol 2002; 46(4):385–391.PubMedGoogle Scholar
  20. 20.
    Hutson LD, Jurynec MJ, Yeo SY et al. Two divergent slit1 genes in zebrafish. Dev Dyn 2003; 228(3):358–369.PubMedGoogle Scholar
  21. 21.
    Wang KH, Brose K, Arnott D et al. Biochemical purification of a mammalian Slit protein as a positive regulator of sensory axon elongation and branching. Cell 1999 96:771–784.PubMedGoogle Scholar
  22. 22.
    Patel K, Nash JAB, Itoh A et al. Slit proteins are dominant chemorepellents for olfactory tract and spinal motor axons. Development 2001; 128:5031–5037.PubMedGoogle Scholar
  23. 23.
    Whitford KL, Dijkhuizen P, Polleux F et al. Molecular control of cortical dendrite development. Annu Rev Neurosci 2002; 25:127–149.PubMedGoogle Scholar
  24. 24.
    Nguyen Ba-Charvet KT, Brose K, Ma L et al. Diversity and specificity of actions of Slit2 proteolytic fragments in axon guidance. J Neurosci 2001; 21:4281–4289.PubMedGoogle Scholar
  25. 25.
    Battye R, Stevens A, Jacobs JR. Axon repulsion from the midline of the Drosophila CNS requires slit function. Development 1999; 126:2475–2481.PubMedGoogle Scholar
  26. 26.
    Chen JH, Wen L, Dupuis S et al. The N-terminal leucine-rich regions in slit are sufficient to repel olfactory bulb axons and subventricular zone neurons. J Neurosci 2001; 21:1548–1556.PubMedGoogle Scholar
  27. 27.
    Howitt JA, Clout NJ, Hohenester E. Binding site for Robo receptors revealed by dissection of the leucine-rich repeat region of Slit. EMBO J 2004; 23(22):4406–4412.PubMedGoogle Scholar
  28. 28.
    Seeger M, Tear G, Ferres-Marco D et al. Mutations affecting growth cone guidance in drosophila: Genes necessary for guidance toward or away from the midline. Neuron 1993; 10(3):409–426.PubMedGoogle Scholar
  29. 29.
    Kidd T, Brose K, Mitchell KJ et al. Roundabout controls axon crossing of the CNS midline and defines a novel subfamily of evolutionarily conserved guidance receptors. Cell 1998; 92:205–215.PubMedGoogle Scholar
  30. 30.
    Rajagopalan S, Vivancos V, Nicolas E et al. Selecting a longitudinal pathway: Robo receptors specify the lateral position of axons in the Drosophila CNS. Cell 2000; 103:1033–1045.PubMedGoogle Scholar
  31. 31.
    Yuan W, Zhou L, Chen JH et al. The mouse SLIT family: Secreted ligands for ROBO expressed in patterns that suggest a role in morphogenesis and axon guidance. Dev Biol 1999; 212:290–306.PubMedGoogle Scholar
  32. 32.
    Lee JS, Ray R, Chien CB. Cloning and expression of three zebrafish roundabout homologs suggest roles in axon guidance and cell migration. Dev Dyn 2001; 221(2):216–230.PubMedGoogle Scholar
  33. 33.
    Jen JC, Chan WM, Bosley TM et al. Mutations in a human ROBO gene disrupt hindbrain axon pathway crossing and morphogenesis. Science 2004; 304(5676):1509–1513.PubMedGoogle Scholar
  34. 34.
    Huminiecki L, Gorn M, Suchting S et al. Magic roundabout is a new member of the roundabout receptor family that is endothelial specific and expressed at sites of active angiogenesis. Genomics 2002; 79(4):547–552.PubMedGoogle Scholar
  35. 35.
    Bedell VM, Yeo SY, Park KW et al. Roundabout4 is essential for angiogenesis in vivo. Proc Natl Acad Sci USA 2005; 102(18):6373–6378.PubMedGoogle Scholar
  36. 36.
    Park KW, Morrison CM, Sorensen LK et al. Robo4 is a vascular-specific receptor that inhibits endothelial migration. Dev Biol 2003; 261:251–267.PubMedGoogle Scholar
  37. 37.
    Suchting S, Heal P, Tahtis K et al. Soluble Robo4 receptor inhibits in vivo angiogenesis and endothelial cell migration. FASEB J 2005; 19(1):121–123.PubMedGoogle Scholar
  38. 38.
    Bashaw GJ, Kidd T, Murray D et al. Repulsive axon guidance: Abelson and enabled play opposing roles downstream of the roundabout receptor. Cell 2000; 101:703–715.PubMedGoogle Scholar
  39. 39.
    Yuan S-SF, Cox LA, Dasika GK et al. Cloning and functional studies of a novel gene aberrantly expressed in RB-deficient embryos. Dev Biol 1999; 207:62–75.PubMedGoogle Scholar
  40. 40.
    Simpson JH, Bland KS, Fetter RD et al. Short-range and long-range guidance by slit and its robo receptors: A combinatorial code of Robo receptors controls lateral position. Cell 2000; 103:1019–1032.PubMedGoogle Scholar
  41. 41.
    Sabatier C, Plump AS, Le M et al. The divergent robo family protein rig-1/robo3 is a negative regulator of slit responsiveness required for midline crossing by commissural axons. Cell 2004; 117(2):157–169.PubMedGoogle Scholar
  42. 42.
    Xian J, Clark KJ, Fordham R et al. Inadequate lung development and bronchial hyperplasia in mice with a targeted deletion in the Dutt1/Robo1 gene. Proc Natl Acad Sci USA 2001; 4:4.Google Scholar
  43. 43.
    Xian J, Aitchison A, Bobrow L et al. Targeted disruption of the 3p12 gene, Dutt1/Robo1, predisposes mice to lung adenocarcinomas and lymphomas with methylation of the gene promoter. Cancer Res 2004; 64(18):6432–6437.PubMedGoogle Scholar
  44. 44.
    Hivert B, Liu Z, Chuang JY et al. Robo1 and Robo2 are hompohilic binding molecules that promote axonal growth. Mol Cell Neurosci 2002; 21:534–545.PubMedGoogle Scholar
  45. 45.
    Liu Z, Patel K, Schmidt H et al. Extracellular Ig domains 1 and 2 of Robo are important for ligand (Slit) binding. Mol Cell Neurosci 2004; 26(2):232–240.PubMedGoogle Scholar
  46. 46.
    Liang Y, Annan RS, Carr SA et al. Mammalian homologues of the Drosophila slit protein are ligands of the heparan sulfate proteoglycan glypican-1 in brain. J Biol Chem 1999; 274(25):17885–17892.PubMedGoogle Scholar
  47. 47.
    Ronca F, Andersen JS, Paech V et al. Characterization of Slit protein interactions with glypican-1. J Biol Chem 2001; 276:29141–29147.PubMedGoogle Scholar
  48. 48.
    Hu H. Cell-surface heparan sulfate is involved in the repulsive guidance activities of Slit2 protein. Nature Neurosci 2001; 4:695–701.PubMedGoogle Scholar
  49. 49.
    Steigemann P, Molitor A, Fellert S et al. Heparan sulfate proteoglycan syndecan promotes axonal and myotube guidance by Slit/Robo signaling. Curr Biol 2004; 14:225–230.PubMedGoogle Scholar
  50. 50.
    Inatani M, Irie F, Plump AS et al. Mammalian brain morphogenesis and midline axon guidance require heparan sulfate. Science 2003; 302(5647):1044–1046.PubMedGoogle Scholar
  51. 51.
    Bashaw GJ, Goodman CS. Chimeric axon guidance receptors: The cytoplasmic domains of slit and netrin receptors specificity attraction versus repulsion. Neuron 1999; 97:917–926.Google Scholar
  52. 52.
    Yu TW, Hao JC, Lim W et al. Shared receptors in axon guidance: SAX-3/Robo signals via UNC-34/Enabled and a Netrin-independent UNC-40/DCC function. Nat Neurosci 2002; 5(11):1147–1154.PubMedGoogle Scholar
  53. 53.
    Wills Z, Emerson M, Rusch J et al. A Drosophila homolog of cyclase-associated proteins collaborates with the Abl tyrosine kinase to control midline axon pathfinding. Neuron 2002; 36(4):611–622.PubMedGoogle Scholar
  54. 54.
    Hsouna A, Kim YS, VanBerkum MF. Abelson tyrosine kinase is required to transduce midline repulsive cues. J Neurobiol 2003; 57(1):15–30.PubMedGoogle Scholar
  55. 55.
    Rhee J, Mahfooz NS, Arregui C et al. Activation of the repulsive receptor Roundabout inhibits N-cadherin-mediated cell adhesion. Nat Cell Biol 2002; 4(10):798–805.PubMedGoogle Scholar
  56. 56.
    Lee H, Engel U, Rusch J et al. The microtubule plus end tracking protein Orbit/MAST/CLASP acts downstream of the tyrosine kinase Abl in mediating axon guidance. Neuron 2004; 42(6):913–926.PubMedGoogle Scholar
  57. 57.
    Huber AB, Kolodkin AL, Ginty DD et al. Signaling at the growth cone: Ligand-receptor complexes and the control of axon growth and guidance. Annu Rev Neurosci 2003; 26:509–563.PubMedGoogle Scholar
  58. 58.
    Bashaw GJ, Hu H, Nobes CD et al. A novel Dbl family RhoGEF promotes Rho-dependent axon attractin to the central nervous system midline in Drosophila and overcomes Robo repulsion. JCB 2001; 155:1117–1122.Google Scholar
  59. 59.
    Matsuura R, Tanaka H, Go MJ. Distinct functions of Rac1 and Cdc42 during axon guidance and growth cone morphogenesis in Drosophila. Eur J Neurosci 2004; 19(1):21–31.PubMedGoogle Scholar
  60. 60.
    Wong K, Ren XR, Huang YZ et al. Signal transduction in neuronal migration. roles of gtpase activating proteins and the small gtpase cdc42 in the slit-robo pathway. Cell 2001; 107(2):209–221.PubMedGoogle Scholar
  61. 61.
    Fan X, Labrador JP, Hing H et al. Slit stimulation recruits Dock and Pak to the roundabout receptor and increases Rac activity to regulate axon repulsion at the CNS midline. Neuron 2003; 40(1):113–127.PubMedGoogle Scholar
  62. 62.
    Stevens A, Jacobs JR. Integrins regulate responsiveness to slit repellent signals. J Neurosci 2002; 22(11):4448–4455.PubMedGoogle Scholar
  63. 63.
    Endris V, Wogatzky B, Leimer U et al. The novel Rho-GTPase activating gene MEGAP/ srGAP3 has a putative role in severe mental retardation. Proc Natl Acad Sci USA 2002; 99(18):11754–11759.PubMedGoogle Scholar
  64. 64.
    Lundstrom A, Gallio M, Englund C et al. Vilse, a conserved Rac/Cdc42 GAP mediating Robo repulsion in tracheal cells and axons. Genes Dev 2004; 18(17):2161–2171.PubMedGoogle Scholar
  65. 65.
    Hu H, Li M, Labrador JP et al. Cross GTPase-activating protein (CrossGAP)/Vilse links the Roundabout receptor to Rac to regulate midline repulsion. Proc Natl Acad Sci USA 2005; 102(12):4613–4618.PubMedGoogle Scholar
  66. 66.
    Stein E, Tessier-Lavigne M. Hierarchical organization of guidance receptors: Silencing of netrin attraction by slit through a Robo/DCC receptor complex. Science 2001; 291(5510):1928–1938.PubMedGoogle Scholar
  67. 67.
    Höpker VH, Shewan D, Tessier-Lavigne M et al. Growth-cone attraction to netrin-1 is converted to repulsion by laminin-1. Nature 1999; 401:69–73.PubMedGoogle Scholar
  68. 68.
    Song H, Ming G, He Z et al. Conversion of neuronal growth cone responses from repulsion to attraction by cyclic nucleotides. Science 1998; 281 (5382):1515–1518.PubMedGoogle Scholar
  69. 69.
    Chalsani SH, Sabelko KA, Sunshine MJ et al. A chemokine, SDF-1, reduces the effectiveness of multiple axonal repellents and is required for normal axon pathfinding. J Neurosci 2003; 23(4):1360–1371.Google Scholar
  70. 70.
    Xu HT, Yuan XB, Guan CB et al. Calcium signaling in chemorepellant Slit2-dependent regulation of neuronal migration. Proc Natl Acad Sci USA 2004; 101(12):4296–4301.PubMedGoogle Scholar
  71. 71.
    Nguyen-Ba-Charvet KT, Brose K, Marillat V et al. Sensory axons response to substrate-bound Slit2 is modulated by laminin and cyclicGMP. Mol Cell Neurosci 2001; 17:1048–1058.PubMedGoogle Scholar
  72. 72.
    Sun Q, Bahri S, Schmid A et al. Receptor tyrosine phosphatases regulate axon guidance across the midline of the drosophila embryo. Development 2000;127:801–812.PubMedGoogle Scholar
  73. 73.
    Fritz JL, VanBerkum MFA. Calmodulin and son of sevenless dependent signaling pathways regulate midline crossing of axons in the Drosophila CNS. Development 2000; 127:1991–2000.PubMedGoogle Scholar
  74. 74.
    Crowner D, Madden K, Goeke S et al. Lola regulates midline crossing of CNS axons in Drosophila. Development 2002; 129(6):1317–1325.PubMedGoogle Scholar
  75. 75.
    Ma Y, Certel K, Gao Y et al. Function interactions between Drosophila bHLH/PAS, Sox, and POU transcription factors regulate CNS midline expression of the slit gene. J Neurosci 2000; 20(12):4596–4605.PubMedGoogle Scholar
  76. 76.
    Wharton Jr K, Franks RG, Kasai Y et al. Control of CNS midline transcription by asymetric E-box-like elements: Similarity to xenobiotic responsive regulation. Development 1994; 120(12):3563–3569.PubMedGoogle Scholar
  77. 77.
    Jin Z, Zhang J, Klar A et al. Irx4-mediated regulation of Slit1 expression contributes to the definition of early axonal paths inside the retina. Development 2003; 130:1037–1048.PubMedGoogle Scholar
  78. 78.
    Yeo SY, Miyashita T, Fricke C et al. Involvement of Islet-2 in the Slit signaling for axonal branching and defasciculation of the sensory neurons in embryonic zebrafish. Mech Dev 2004; 121(4):315–324.PubMedGoogle Scholar
  79. 79.
    Miyarhita T, Yeo SY, Hirate Y et al. Plexin A4 is necessary as a downstream target of Islet2 to mediate Slit signaling for promotion of sensory axon branching. Development 2004; 131(15):3705–3715.Google Scholar
  80. 80.
    Zlatic M, Landgraf M, Bate M. Genetic specification of axonal arbors. Atonal regulates robo3 to position terminal branches in the Drosophila nervous system., Neuron 2003; 37(1):41–51.PubMedGoogle Scholar
  81. 81.
    Kraut R, Zinn K. Roundabout 2 regulates migration of sensory neurons by signaling in trans. Curr Biol 2004;14(15):1319–1329.PubMedGoogle Scholar
  82. 82.
    Kidd T, Russell C, Goodman CS et al. Dosage-sensitive and complementary functions of roudabout and commissureless control axon crossing of the CNS midline. Neuron 1998; 20:25–33.PubMedGoogle Scholar
  83. 83.
    Tear G, Harris R, Sutaria S et al. Commissureless controls growth cone guidance across the CNS midline in Drosophila and encodes a novel membrane protein. Neuron 1996; 16(3):501–514.PubMedGoogle Scholar
  84. 84.
    Georgiou M, Tear G. Commissureless is required both in commissural neurones and midline cells for axon guidance across the midline. Development 2002; 129(12):2947–2956.PubMedGoogle Scholar
  85. 85.
    Keleman K, Rajagopalan S, Cleppien D et al. Comm sorts robo to control axon guidance at the Drosophila midline. Cell 2002; 110(4):415.PubMedGoogle Scholar
  86. 86.
    Keleman K, Ribeiro C, Dickson BJ. Comm function in commissural axon guidance: Cell-autonomous sorting of Robo in vivo. Nat Neurosci 2005; 8(2):156–163.PubMedGoogle Scholar
  87. 87.
    Georgiou M, Tear G. The N-terminal and transmembrane domains of Commissureless are necessary for its function and trafficking within neurons. Mech Dev 2003; 120(9):1009–1019.PubMedGoogle Scholar
  88. 88.
    Myat A, Henry P, McCabe V et al. Drosophila Nedd4, a ubiquitin ligase, is recruited by Commissureless to control cell surface levels of the roundabout receptor. Neuron 2002; 35(3):447–459.PubMedGoogle Scholar
  89. 89.
    Zou Y, Stoeckli E, Chen H et al. Squeezing axons out of the gray matter: A role for slit and semaphorin proteins from the midline and ventral spinal cord. 2000; 102:363–375.Google Scholar
  90. 90.
    Long H, Sabatier C, Le M et al. Conserved roles for slit and robo proteins in midline commissural axon guidance. Neuron 2004; 42(2):213–223.PubMedGoogle Scholar
  91. 91.
    Marillat V, Sabatier C, Failli V et al. The Slit receptor Rig-1/Robo3 controls midline crossing by hindbrain precerebellar neurons and axons. Neuron 2004;43:1–20.Google Scholar
  92. 92.
    Schimmelpfeng K, Gogel S, Klambt C. The function of leak and kuzbanian during growth cone and cell migration Mech Dev 2001; 106(1–2):25–36.PubMedGoogle Scholar
  93. 93.
    Onel S, Bolke L, Klambt C. The Drosophila ARF6-GEF Schizo controls commissure formation by regulating Slit. Development 2004; 131(11):2587–2594.PubMedGoogle Scholar
  94. 94.
    Jhaveri D, Saharan S, Sen A et al. Positioning sensory terminals in the olfactory lobe of Drosophila by Robo signaling. Development 2004; 131(9):1903–1912.PubMedGoogle Scholar
  95. 95.
    Plump AS, Erskine L, Sabatier C et al. Slit1 and Slit2, cooperate to prevent premature midline crossing of retinal axons in the mouse visual system. Neuron 2002; 33:219–232.PubMedGoogle Scholar
  96. 96.
    Hutson LD, Chien CB. Pathfinding and error correction by retinal axons: The role of astray/robo2. Neuron 2002; 33(2):205–217.PubMedGoogle Scholar
  97. 97.
    Nguyen-Ba-Charvet KT, Plump AS, Tessier-lavigne M et al. Slit 1and Slit2 proteins control the development of the lateral olfactory tract. J Neurosci 2002;22:5473–5480.PubMedGoogle Scholar
  98. 98.
    Bagri A, Marin O, Plump AS et al. Slit proteins prevent midline crossing and determine the dorsoventral position of major axonal pathways in the mammalian forebrain. Neuron 2002; 33:233–248.PubMedGoogle Scholar
  99. 99.
    Shu T, Sundaresan V, McCarthy MM et al. Slit2 guides both precrossing and postcrossing callosal axons at the midline in vivo. J Neurosci 2003; 23 (22):8176–8184.PubMedGoogle Scholar
  100. 100.
    Fricke C, Lee J-S, Geiger-Rudolph S et al. Astray, a zebrafish roundabout homolog required for retinal axon guidance. Science 2001; 292:507–510.PubMedGoogle Scholar
  101. 101.
    Marillat V, Cases O, Nguyen-Ba-Charvet KT et al. Spatiotemporal expression patterns of slit and robo genes in the rat brain. J Comp Neurol 2002; 442:130–155.PubMedGoogle Scholar
  102. 102.
    Tayler TD, Robichaux MB, Garrity PA. Compartmentalization of visual centers in the Drosophila brain requires Slit and Robo proteins. Development 2004; 131(23):5935–5945.PubMedGoogle Scholar
  103. 103.
    Knoll B, Schmidt H, Andrews W et al. On the topographic targeting of basal vomeronasal axons through Slit-mediated chemorepulsion Development 2003; 130:5073–5082.PubMedGoogle Scholar
  104. 104.
    Cloutier JF, Sahay A, Chang EC et al. Differential requirements for semaphorin 3F and Slit-1 in axonal targeting, fasciculation, and segregation of olfactory sensory neuron projections. J Neurosci 2004; 24(41):9087–9096.PubMedGoogle Scholar
  105. 105.
    Miyasaka N, Sato Y, Yeo SY et al. Robo2 is required for establishment of a precise glomerular map in the zebrafish olfactory system. Development 2005; 132:1283–1293.PubMedGoogle Scholar
  106. 106.
    Ozdinler PH, Erzurumlu RS. Slit2, a branching-arborization factor for sensory axons in the Mammalian CNS. J Neurosci 2002; 22(11):4540–4549.PubMedGoogle Scholar
  107. 107.
    Furrer MP, Kim S, Wolf B et al. Robo and Frazzled/DCC mediate dendritic guidance at the CNS midline. Nat Neurosci 2003; 6(3):223–230.PubMedGoogle Scholar
  108. 108.
    Whitford KL, Marillat V, Stein E et al. Regulation of cortical dendrite development by Slit-Robo interactions. Neuron 2002; 33:47–61.PubMedGoogle Scholar
  109. 109.
    Couch JA, Chen J, Rieff HI et al. Robo2 and robo3 interact with eagle to regulate serotonergic neuron differentiation. Development 2004; 131(5):997–1006.PubMedGoogle Scholar
  110. 110.
    Mehta B, Bhat KM. Slit signaling promotes the terminal asymmetric division of neural precursor cells in the Drosophila CNS. Development 2001; 128(16):3161–3168.PubMedGoogle Scholar
  111. 111.
    Connor RM, Key B. Expression and role of Roundabout-1 in embryonic Xenopus forebrain. Dev Dyn 2002; 225(1):22–34.PubMedGoogle Scholar
  112. 112.
    Grieshammer U, Ma L, Plump AS et al. SLIT2-mediated ROBO2 signaling restricts kidney induction to a single site. Dev Cell 2004; 6(5):709–717.PubMedGoogle Scholar
  113. 113.
    Kinrade EFV, Bartes T, Tear G et al. Roudabout signalling, cell contact and trophic support confine longitudinal glia and axons in the Drosophila CNS. Development 2001; 128:207–216.PubMedGoogle Scholar
  114. 114.
    Kramer SG, Kidd T, Simpson JH et al. Switching repulsion to attraction: Changing responses to slit during transition in mesoderm migration. Science 2001; 292:737–740.PubMedGoogle Scholar
  115. 115.
    Englund C, Steneberg P, Falileeva L et al. Attractive and repulsive functions of Slit are mediated by different receptors in the Drosophila trachea. Development 2002; 129(21):4941–4951.PubMedGoogle Scholar
  116. 116.
    Doetsch F. The glial identity of neural stem cells. Nat Neurosci 2003; 6(11):1127–1134.PubMedGoogle Scholar
  117. 117.
    Hu H, Rutishauser U. A septum-derived chemorepulsive factor for migrating olfactory interneuron precursors. Neuron 1996; 16:933–940.PubMedGoogle Scholar
  118. 118.
    Wu W, Wong K, Chen JH et al. Directional guidance of neuronal migration in the olfactory system by the protein Slit. Nature 1999; 400:331–336.PubMedGoogle Scholar
  119. 119.
    Nguyen-Ba-Charvet KT, Picard-Riera N, Tessier-Lavigne M et al. Multiple roles for slits in the control of cell migration in the rostral migratory stream. J Neurosci 2004; 24(6):1497–1506.PubMedGoogle Scholar
  120. 120.
    Ward M, McCann C, DeWulf M et al. Distinguishing between directional guidance and motility regulation in neuronal migration. J Neurosci 2003; 23(12):5170–5177.PubMedGoogle Scholar
  121. 121.
    Mason HA, Ito S, Corfas G. Extracellular signals that regulate the tangential migration of olfactory bulb neuronal precursors: Inducers, inhibitors, and repellents. J Neurosci 2001; 21:7654–7663.PubMedGoogle Scholar
  122. 122.
    De Bellard ME, Rao Y, Bronner-Fraser M. Dual function of Slit2 in repulsion and enhanced migration of trunk, but not vagal, neural crest cells. J Cell Biol 2003; 162(2):269–279.PubMedGoogle Scholar
  123. 123.
    Zhu Y, Li HS, Zhou L et al. Cellular and molecular guidance of GABAergic neuronal migration from an extracortical origin to the neocortex. Neuron 1999; 23:473–485.PubMedGoogle Scholar
  124. 124.
    Marin O, Plump AS, Flames N et al. Directional guidance of interneuron migration to the cerebral cortex relies on subcortical Slit 1/2-independent repulsion and cortical attraction. Development 2003; 130:1889–1901.PubMedGoogle Scholar
  125. 125.
    Causeret F, Danne F, Ezan F et al. Slit antagonizes netrin-1 attractive effects during the migration of inferior olivary neurons. Dev Biol 2002; 246(2):429–440.PubMedGoogle Scholar
  126. 126.
    Wu JY, Feng L, Park H-T et al. The neuronal repellent Slit inhibits leukocyte chemotaxis induced by chemotactic factors. Nature 2001; 410:948–952.PubMedGoogle Scholar
  127. 127.
    Wang B, Xiao Y, Ding BB et al. Induction of tumor angiogenesis by Slit-Robo signaling and inhibition of cancer growth by blocking Robo activity. Cancer Cell 2003; 4(1):19–29.PubMedGoogle Scholar
  128. 128.
    Chédotal A, Kerjan G, Moreau-Fauvarque C. The brain within the tumor: New role for axon guidance molecules in cancer. Cell Death Differ 2005; 12(8):1044–1056.PubMedGoogle Scholar
  129. 129.
    Filbin MT. Myelin-associated inhibitors of axonal regeneration in the adult mammalian CNS. Nat Rev Neurosci 2003; 4(9):703–713.PubMedGoogle Scholar
  130. 130.
    Hagino S, Iseki K, Mori T et al. Slit and glypican-1 mRNAs are coexpressed in the reactive astrocytes of the injured adult brain. Glia 2003; 42(2):130–138.PubMedGoogle Scholar
  131. 131.
    Bloechlinger S, Karchewski LA, Woolf CJ. Dynamic changes in glypican-1 expression in dorsal root ganglion neurons after peripheral and central axonal injury. Eur J Neurosci 2004; 19(5):1119–1132.PubMedGoogle Scholar
  132. 132.
    Madura T, Yamashita T, Kubo T et al. Changes in mRNA of Slit-Robo GTPase-activating protein 2 following facial nerve transection. Brain Res Mol Brain Res 2004; 123(1–2):76–80.PubMedGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2007

Authors and Affiliations

  • Alain Chédotal
    • 1
  1. 1.CNRS UMR 7102Université Paris 6ParisFrance

Personalised recommendations