Cellular and Molecular Life Sciences

, Volume 68, Issue 15, pp 2539–2553 | Cite as

Axonal commissures in the central nervous system: how to cross the midline?



Organisms with bilateral symmetry elaborate patterns of neuronal projections connecting both sides of the central nervous system at all levels of the neuraxis. During development, these so-called commissural projections navigate across the midline to innervate their contralateral targets. Commissural axon pathfinding has been extensively studied over the past years and turns out to be a highly complex process, implicating modulation of axon responsiveness to the various guidance cues that instruct axon trajectories towards, within and away from the midline. Understanding the molecular mechanisms allowing these switches of response to take place at the appropriate time and place is a major challenge for current research. Recent work characterized several instructive processes controlling the spatial and temporal fine-tuning of the guidance molecular machinery. These findings illustrate the molecular strategies by which commissural axons modulate their sensitivity to guidance cues during midline crossing and show that regulation at both transcriptional and post-transcriptional levels are crucial for commissural axon guidance.


Central nervous system Molecular strategies Commissural axon pathfinding Midline crossing 



We acknowledge E. A. Derrington for helpful comments and manuscript reading. VC is supported by the "Fondation pour la Recherche Médicale (FRM) and the "Agence Nationale pour la Recherche" ANR.


  1. 1.
    Black DL, Zipursky SL (2008) To cross or not to cross: alternatively spliced forms of the Robo3 receptor regulate discrete steps in axonal midline crossing. Neuron 58(3):297–298PubMedGoogle Scholar
  2. 2.
    Dickson BJ, Gilestro GF (2006) Regulation of commissural axon pathfinding by slit and its Robo receptors. Annu Rev Cell Dev Biol 22:651–675PubMedGoogle Scholar
  3. 3.
    Evans TA, Bashaw GJ (2010) Axon guidance at the midline: of mice and flies. Curr Opin Neurobiol 20(1):79–85PubMedGoogle Scholar
  4. 4.
    Shirasaki R, Katsumata R, Murakami F (1998) Change in chemoattractant responsiveness of developing axons at an intermediate target. Science 279(5347):105–107PubMedGoogle Scholar
  5. 5.
    Brose K, Bland KS, Wang KH, Arnott D, Henzel W, Goodman CS, Tessier-Lavigne M, Kidd T (1999) Slit proteins bind Robo receptors and have an evolutionarily conserved role in repulsive axon guidance. Cell 96(6):795–806PubMedGoogle Scholar
  6. 6.
    Butler SJ, Dodd J (2003) A role for BMP heterodimers in roof plate-mediated repulsion of commissural axons. Neuron 38(3):389–401PubMedGoogle Scholar
  7. 7.
    Charron F, Stein E, Jeong J, McMahon AP, Tessier-Lavigne M (2003) The morphogen sonic hedgehog is an axonal chemoattractant that collaborates with netrin-1 in midline axon guidance. Cell 113(1):11–23PubMedGoogle Scholar
  8. 8.
    Fazeli A, Dickinson SL, Hermiston ML, Tighe RV, Steen RG, Small CG, Stoeckli ET, Keino-Masu K, Masu M, Rayburn H, Simons J, Bronson RT, Gordon JI, Tessier-Lavigne M, Weinberg RA (1997) Phenotype of mice lacking functional Deleted in colorectal cancer (Dcc) gene. Nature 386(6627):796–804PubMedGoogle Scholar
  9. 9.
    Gore BB, Wong KG, Tessier-Lavigne M (2008) Stem cell factor functions as an outgrowth-promoting factor to enable axon exit from the midline intermediate target. Neuron 57(4):501–510PubMedGoogle Scholar
  10. 10.
    Jevince AR, Kadison SR, Pittman AJ, Chien CB, Kaprielian Z (2006) Distribution of EphB receptors and ephrin-B1 in the developing vertebrate spinal cord. J Comp Neurol 497(5):734–750PubMedGoogle Scholar
  11. 11.
    Kadison SR, Makinen T, Klein R, Henkemeyer M, Kaprielian Z (2006) EphB receptors and ephrin-B3 regulate axon guidance at the ventral midline of the embryonic mouse spinal cord. J Neurosci 26(35):8909–8914PubMedGoogle Scholar
  12. 12.
    Kullander K, Klein R (2002) Mechanisms and functions of Eph and ephrin signalling. Nat Rev Mol Cell Biol 3(7):475–486PubMedGoogle Scholar
  13. 13.
    Ly A, Nikolaev A, Suresh G, Zheng Y, Tessier-Lavigne M, Stein E (2008) DSCAM is a netrin receptor that collaborates with DCC in mediating turning responses to netrin-1. Cell 133(7):1241–1254PubMedGoogle Scholar
  14. 14.
    Lyuksyutova AI, Lu CC, Milanesio N, King LA, Guo N, Wang Y, Nathans J, Tessier-Lavigne M, Zou Y (2003) Anterior-posterior guidance of commissural axons by Wnt-frizzled signaling. Science 302(5652):1984–1988PubMedGoogle Scholar
  15. 15.
    Matsumoto Y, Irie F, Inatani M, Tessier-Lavigne M, Yamaguchi Y (2007) Netrin-1/DCC signaling in commissural axon guidance requires cell-autonomous expression of heparan sulfate. J Neurosci 27(16):4342–4350PubMedGoogle Scholar
  16. 16.
    Nawabi H, Briancon-Marjollet A, Clark C, Sanyas I, Takamatsu H, Okuno T, Kumanogoh A, Bozon M, Takeshima K, Yoshida Y, Moret F, Abouzid K, Castellani V (2010) A midline switch of receptor processing regulates commissural axon guidance in vertebrates. Genes Dev 24(4):396–410PubMedGoogle Scholar
  17. 17.
    Okada A, Charron F, Morin S, Shin DS, Wong K, Fabre PJ, Tessier-Lavigne M, McConnell SK (2006) Boc is a receptor for sonic hedgehog in the guidance of commissural axons. Nature 444(7117):369–373PubMedGoogle Scholar
  18. 18.
    Serafini T, Colamarino SA, Leonardo ED, Wang H, Beddington R, Skarnes WC, Tessier-Lavigne M (1996) Netrin-1 is required for commissural axon guidance in the developing vertebrate nervous system. Cell 87(6):1001–1014PubMedGoogle Scholar
  19. 19.
    Stoeckli ET, Landmesser LT (1995) Axonin-1, Nr-CAM, and Ng-CAM play different roles in the in vivo guidance of chick commissural neurons. Neuron 14(6):1165–1179PubMedGoogle Scholar
  20. 20.
    Stoeckli ET, Sonderegger P, Pollerberg GE, Landmesser LT (1997) Interference with axonin-1 and NrCAM interactions unmasks a floor-plate activity inhibitory for commissural axons. Neuron 18(2):209–221PubMedGoogle Scholar
  21. 21.
    Zou Y, Stoeckli E, Chen H, Tessier-Lavigne M (2000) Squeezing axons out of the gray matter: a role for slit and semaphorin proteins from midline and ventral spinal cord. Cell 102(3):363–375PubMedGoogle Scholar
  22. 22.
    Kidd T, Bland KS, Goodman CS (1999) Slit is the midline repellent for the robo receptor in Drosophila. Cell 96(6):785–794PubMedGoogle Scholar
  23. 23.
    Bourikas D, Pekarik V, Baeriswyl T, Grunditz A, Sadhu R, Nardo M, Stoeckli ET (2005) Sonic hedgehog guides commissural axons along the longitudinal axis of the spinal cord. Nat Neurosci 8(3):297–304. doi:10.1038/nn1396 PubMedGoogle Scholar
  24. 24.
    Winckler B, Mellman I (2010) Trafficking guidance receptors. Cold Spring Harb Perspect Biol 2(7):a001826PubMedGoogle Scholar
  25. 25.
    Keleman K, Rajagopalan S, Cleppien D, Teis D, Paiha K, Huber LA, Technau GM, Dickson BJ (2002) Comm sorts robo to control axon guidance at the Drosophila midline. Cell 110(4):415–427PubMedGoogle Scholar
  26. 26.
    Keleman K, Ribeiro C, Dickson BJ (2005) Comm function in commissural axon guidance: cell-autonomous sorting of Robo in vivo. Nat Neurosci 8(2):156–163PubMedGoogle Scholar
  27. 27.
    Georgiou M, Tear G (2002) Commissureless is required both in commissural neurones and midline cells for axon guidance across the midline. Development (Cambridge) 129(12):2947–2956Google Scholar
  28. 28.
    Georgiou M, Tear G (2003) The N-terminal and transmembrane domains of Commissureless are necessary for its function and trafficking within neurons. Mech Dev 120(9):1009–1019PubMedGoogle Scholar
  29. 29.
    Stein E, Tessier-Lavigne M (2001) Hierarchical organization of guidance receptors: silencing of netrin attraction by slit through a Robo/DCC receptor complex. Science 291(5510):1928–1938PubMedGoogle Scholar
  30. 30.
    Bashaw GJ, Klein R (2010) Signaling from axon guidance receptors. Cold Spring Harb Perspect Biol 2(5):a001941PubMedGoogle Scholar
  31. 31.
    Kania A, Jessell TM (2003) Topographic motor projections in the limb imposed by LIM homeodomain protein regulation of ephrin-A:EphA interactions. Neuron 38(4):581–596PubMedGoogle Scholar
  32. 32.
    Kania A, Johnson RL, Jessell TM (2000) Coordinate roles for LIM homeobox genes in directing the dorsoventral trajectory of motor axons in the vertebrate limb. Cell 102(2):161–173PubMedGoogle Scholar
  33. 33.
    Petros TJ, Rebsam A, Mason CA (2008) Retinal axon growth at the optic chiasm: to cross or not to cross. Annu Rev Neurosci 31:295–315PubMedGoogle Scholar
  34. 34.
    Drager UC (1985) Birth dates of retinal ganglion cells giving rise to the crossed and uncrossed optic projections in the mouse. Proc R Soc Lond B 224(1234):57–77Google Scholar
  35. 35.
    Guillery RW, Mason CA, Taylor JS (1995) Developmental determinants at the mammalian optic chiasm. J Neurosci 15(7 Pt 1):4727–4737PubMedGoogle Scholar
  36. 36.
    Marcus RC, Mason CA (1995) The first retinal axon growth in the mouse optic chiasm: axon patterning and the cellular environment. J Neurosci 15(10):6389–6402PubMedGoogle Scholar
  37. 37.
    Sretavan DW, Reichardt LF (1993) Time-lapse video analysis of retinal ganglion cell axon pathfinding at the mammalian optic chiasm: growth cone guidance using intrinsic chiasm cues. Neuron 10(4):761–777PubMedGoogle Scholar
  38. 38.
    Wizenmann A, Thanos S, von Boxberg Y, Bonhoeffer F (1993) Differential reaction of crossing and non-crossing rat retinal axons on cell membrane preparations from the chiasm midline: an in vitro study. Development (Cambridge) 117(2):725–735Google Scholar
  39. 39.
    Nakagawa S, Brennan C, Johnson KG, Shewan D, Harris WA, Holt CE (2000) Ephrin-B regulates the Ipsilateral routing of retinal axons at the optic chiasm. Neuron 25(3):599–610PubMedGoogle Scholar
  40. 40.
    Williams SE, Mann F, Erskine L, Sakurai T, Wei S, Rossi DJ, Gale NW, Holt CE, Mason CA, Henkemeyer M (2003) Ephrin-B2 and EphB1 mediate retinal axon divergence at the optic chiasm. Neuron 39(6):919–935PubMedGoogle Scholar
  41. 41.
    Petros TJ, Shrestha BR, Mason C (2009) Specificity and sufficiency of EphB1 in driving the ipsilateral retinal projection. J Neurosci 29(11):3463–3474PubMedGoogle Scholar
  42. 42.
    Herrera E, Brown L, Aruga J, Rachel RA, Dolen G, Mikoshiba K, Brown S, Mason CA (2003) Zic2 patterns binocular vision by specifying the uncrossed retinal projection. Cell 114(5):545–557PubMedGoogle Scholar
  43. 43.
    Merzdorf CS (2007) Emerging roles for zic genes in early development. Dev Dyn 236(4):922–940PubMedGoogle Scholar
  44. 44.
    Garcia-Frigola C, Carreres MI, Vegar C, Mason C, Herrera E (2008) Zic2 promotes axonal divergence at the optic chiasm midline by EphB1-dependent and -independent mechanisms. Development (Cambridge) 135(10):1833–1841Google Scholar
  45. 45.
    Lee R, Petros TJ, Mason CA (2008) Zic2 regulates retinal ganglion cell axon avoidance of ephrinB2 through inducing expression of the guidance receptor EphB1. J Neurosci 28(23):5910–5919PubMedGoogle Scholar
  46. 46.
    Wilson SI, Shafer B, Lee KJ, Dodd J (2008) A molecular program for contralateral trajectory: Rig-1 control by LIM homeodomain transcription factors. Neuron 59(3):413–424PubMedGoogle Scholar
  47. 47.
    Gowan K, Helms AW, Hunsaker TL, Collisson T, Ebert PJ, Odom R, Johnson JE (2001) Crossinhibitory activities of Ngn1 and Math1 allow specification of distinct dorsal interneurons. Neuron 31(2):219–232PubMedGoogle Scholar
  48. 48.
    Gross MK, Dottori M, Goulding M (2002) Lbx1 specifies somatosensory association interneurons in the dorsal spinal cord. Neuron 34(4):535–549PubMedGoogle Scholar
  49. 49.
    Lee KJ, Mendelsohn M, Jessell TM (1998) Neuronal patterning by BMPs: a requirement for GDF7 in the generation of a discrete class of commissural interneurons in the mouse spinal cord. Genes Dev 12(21):3394–3407PubMedGoogle Scholar
  50. 50.
    Helms AW, Johnson JE (2003) Specification of dorsal spinal cord interneurons. Curr Opin Neurobiol 13(1):42–49PubMedGoogle Scholar
  51. 51.
    Bermingham NA, Hassan BA, Wang VY, Fernandez M, Banfi S, Bellen HJ, Fritzsch B, Zoghbi HY (2001) Proprioceptor pathway development is dependent on Math1. Neuron 30(2):411–422PubMedGoogle Scholar
  52. 52.
    Helms AW, Johnson JE (1998) Progenitors of dorsal commissural interneurons are defined by MATH1 expression. Development (Cambridge) 125(5):919–928Google Scholar
  53. 53.
    Kidd T, Brose K, Mitchell KJ, Fetter RD, Tessier-Lavigne M, Goodman CS, Tear G (1998) Roundabout controls axon crossing of the CNS midline and defines a novel subfamily of evolutionarily conserved guidance receptors. Cell 92(2):205–215PubMedGoogle Scholar
  54. 54.
    Kidd T, Russell C, Goodman CS, Tear G (1998) Dosage-sensitive and complementary functions of roundabout and commissureless control axon crossing of the CNS midline. Neuron 20(1):25–33PubMedGoogle Scholar
  55. 55.
    Bonkowsky JL, Yoshikawa S, O’Keefe DD, Scully AL, Thomas JB (1999) Axon routing across the midline controlled by the Drosophila Derailed receptor. Nature 402(6761):540–544PubMedGoogle Scholar
  56. 56.
    Yang L, Garbe DS, Bashaw GJ (2009) A frazzled/DCC-dependent transcriptional switch regulates midline axon guidance. Science 324(5929):944–947PubMedGoogle Scholar
  57. 57.
    Liu QX, Hiramoto M, Ueda H, Gojobori T, Hiromi Y, Hirose S (2009) Midline governs axon pathfinding by coordinating expression of two major guidance systems. Genes Dev 23(10):1165–1170PubMedGoogle Scholar
  58. 58.
    Buescher M, Svendsen PC, Tio M, Miskolczi-McCallum C, Tear G, Brook WJ, Chia W (2004) Drosophila T box proteins break the symmetry of hedgehog-dependent activation of wingless. Curr Biol 14(19):1694–1702PubMedGoogle Scholar
  59. 59.
    Buescher M, Tio M, Tear G, Overton PM, Brook WJ, Chia W (2006) Functions of the segment polarity genes midline and H15 in Drosophila melanogaster neurogenesis. Dev Biol 292(2):418–429PubMedGoogle Scholar
  60. 60.
    Gaziova I, Bhat KM (2009) Ancestry-independent fate specification and plasticity in the developmental timing of a typical Drosophila neuronal lineage. Development (Cambridge) 136(2):263–274Google Scholar
  61. 61.
    Leal SM, Qian L, Lacin H, Bodmer R, Skeath JB (2009) Neuromancer1 and Neuromancer2 regulate cell fate specification in the developing embryonic CNS of Drosophila melanogaster. Dev Biol 325(1):138–150PubMedGoogle Scholar
  62. 62.
    Stennard FA, Harvey RP (2005) T-box transcription factors and their roles in regulatory hierarchies in the developing heart. Development (Cambridge) 132(22):4897–4910Google Scholar
  63. 63.
    Rajagopalan S, Nicolas E, Vivancos V, Berger J, Dickson BJ (2000) Crossing the midline: roles and regulation of Robo receptors. Neuron 28(3):767–777PubMedGoogle Scholar
  64. 64.
    Simpson JH, Kidd T, Bland KS, Goodman CS (2000) Short-range and long-range guidance by slit and its Robo receptors Robo and Robo2 play distinct roles in midline guidance. Neuron 28(3):753–766PubMedGoogle Scholar
  65. 65.
    Spitzweck B, Brankatschk M, Dickson BJ (2010) Distinct protein domains and expression patterns confer divergent axon guidance functions for Drosophila Robo receptors. Cell 140(3):409–420PubMedGoogle Scholar
  66. 66.
    Black DL (2000) Protein diversity from alternative splicing: a challenge for bioinformatics and post-genome biology. Cell 103(3):367–370PubMedGoogle Scholar
  67. 67.
    Craig AM, Kang Y (2007) Neurexin-neuroligin signaling in synapse development. Curr Opin Neurobiol 17(1):43–52PubMedGoogle Scholar
  68. 68.
    Chen Z, Gore BB, Long H, Ma L, Tessier-Lavigne M (2008) Alternative splicing of the Robo3 axon guidance receptor governs the midline switch from attraction to repulsion. Neuron 58(3):325–332PubMedGoogle Scholar
  69. 69.
    Mambetisaeva ET, Andrews W, Camurri L, Annan A, Sundaresan V (2005) Robo family of proteins exhibit differential expression in mouse spinal cord and Robo-Slit interaction is required for midline crossing in vertebrate spinal cord. Dev Dyn 233(1):41–51PubMedGoogle Scholar
  70. 70.
    Sabatier C, Plump AS, Le M, Brose K, Tamada A, Murakami F, Lee EY, Tessier-Lavigne M (2004) The divergent Robo family protein rig-1/Robo3 is a negative regulator of slit responsiveness required for midline crossing by commissural axons. Cell 117(2):157–169PubMedGoogle Scholar
  71. 71.
    Lin AC, Tan CL, Lin CL, Strochlic L, Huang YS, Richter JD, Holt CE (2009) Cytoplasmic polyadenylation and cytoplasmic polyadenylation element-dependent mRNA regulation are involved in Xenopus retinal axon development. Neural Dev 4:8PubMedGoogle Scholar
  72. 72.
    Richter JD (2007) CPEB: a life in translation. Trends Biochem Sci 32(6):279–285PubMedGoogle Scholar
  73. 73.
    Bassell GJ, Warren ST (2008) Fragile X syndrome: loss of local mRNA regulation alters synaptic development and function. Neuron 60(2):201–214. doi:10.1016/j.neuron.2008.10.004 PubMedGoogle Scholar
  74. 74.
    Kuwako K, Kakumoto K, Imai T, Igarashi M, Hamakubo T, Sakakibara S, Tessier-Lavigne M, Okano HJ, Okano H (2010) Neural RNA-binding protein Musashi1 controls midline crossing of precerebellar neurons through posttranscriptional regulation of Robo3/Rig-1 expression. Neuron 67(3):407–421PubMedGoogle Scholar
  75. 75.
    Di Meglio T, Nguyen-Ba-Charvet KT, Tessier-Lavigne M, Sotelo C, Chedotal A (2008) Molecular mechanisms controlling midline crossing by precerebellar neurons. J Neurosci 28(25):6285–6294PubMedGoogle Scholar
  76. 76.
    Kuhl D, Skehel P (1998) Dendritic localization of mRNAs. Curr Opin Neurobiol 8(5):600–606PubMedGoogle Scholar
  77. 77.
    Martin KC, Barad M, Kandel ER (2000) Local protein synthesis and its role in synapse-specific plasticity. Curr Opin Neurobiol 10(5):587–592PubMedGoogle Scholar
  78. 78.
    Steward O (1997) mRNA localization in neurons: a multipurpose mechanism? Neuron 18(1):9–12PubMedGoogle Scholar
  79. 79.
    Steward O, Levy WB (1982) Preferential localization of polyribosomes under the base of dendritic spines in granule cells of the dentate gyrus. J Neurosci 2(3):284–291PubMedGoogle Scholar
  80. 80.
    Davis L, Dou P, De Wit M, Kater SB (1992) Protein synthesis within neuronal growth cones. J Neurosci 12(12):4867–4877PubMedGoogle Scholar
  81. 81.
    Campbell DS, Holt CE (2001) Chemotropic responses of retinal growth cones mediated by rapid local protein synthesis and degradation. Neuron 32(6):1013–1026PubMedGoogle Scholar
  82. 82.
    Merianda TT, Lin AC, Lam JS, Vuppalanchi D, Willis DE, Karin N, Holt CE, Twiss JL (2009) A functional equivalent of endoplasmic reticulum and Golgi in axons for secretion of locally synthesized proteins. Mol Cell Neurosci 40(2):128–142PubMedGoogle Scholar
  83. 83.
    Horton AC, Ehlers MD (2003) Dual modes of endoplasmic reticulum-to-Golgi transport in dendrites revealed by live-cell imaging. J Neurosci 23(15):6188–6199PubMedGoogle Scholar
  84. 84.
    Zivraj KH, Tung YC, Piper M, Gumy L, Fawcett JW, Yeo GS, Holt CE (2010) Subcellular profiling reveals distinct and developmentally regulated repertoire of growth cone mRNAs. J Neurosci 30(46):15464–15478PubMedGoogle Scholar
  85. 85.
    Lin AC, Holt CE (2007) Local translation and directional steering in axons. EMBO J 26(16):3729–3736PubMedGoogle Scholar
  86. 86.
    Lin AC, Holt CE (2008) Function and regulation of local axonal translation. Curr Opin Neurobiol 18(1):60–68PubMedGoogle Scholar
  87. 87.
    Roche FK, Marsick BM, Letourneau PC (2009) Protein synthesis in distal axons is not required for growth cone responses to guidance cues. J Neurosci 29(3):638–652PubMedGoogle Scholar
  88. 88.
    Hengst U, Deglincerti A, Kim HJ, Jeon NL, Jaffrey SR (2009) Axonal elongation triggered by stimulus-induced local translation of a polarity complex protein. Nat Cell Biol 11(8):1024–1030PubMedGoogle Scholar
  89. 89.
    Dubacq C, Jamet S, Trembleau A (2009) Evidence for developmentally regulated local translation of odorant receptor mRNAs in the axons of olfactory sensory neurons. J Neurosci 29(33):10184–10190PubMedGoogle Scholar
  90. 90.
    Brittis PA, Lu Q, Flanagan JG (2002) Axonal protein synthesis provides a mechanism for localized regulation at an intermediate target. Cell 110(2):223–235PubMedGoogle Scholar
  91. 91.
    Tcherkezian J, Brittis PA, Thomas F, Roux PP, Flanagan JG (2010) Transmembrane receptor DCC associates with protein synthesis machinery and regulates translation. Cell 141(4):632–644PubMedGoogle Scholar
  92. 92.
    Evans TA, Bashaw GJ (2010) Functional diversity of Robo receptor immunoglobulin domains promotes distinct axon guidance decisions. Curr Biol 20(6):567–572PubMedGoogle Scholar
  93. 93.
    Gilestro GF (2008) Redundant mechanisms for regulation of midline crossing in Drosophila. PloS one 3(11):e3798PubMedGoogle Scholar
  94. 94.
    Coleman HA, Labrador JP, Chance RK, Bashaw GJ (2010) The Adam family metalloprotease Kuzbanian regulates the cleavage of the roundabout receptor to control axon repulsion at the midline. Development (Cambridge) 137(14):2417–2426Google Scholar
  95. 95.
    Hattori M, Osterfield M, Flanagan JG (2000) Regulated cleavage of a contact-mediated axon repellent. Science 289(5483):1360–1365PubMedGoogle Scholar
  96. 96.
    Chedotal A (2007) Slits and their receptors. Adv Exp Med Biol 621:65–80PubMedGoogle Scholar
  97. 97.
    Bagnard D, Lohrum M, Uziel D, Puschel AW, Bolz J (1998) Semaphorins act as attractive and repulsive guidance signals during the development of cortical projections. Development (Cambridge) 125(24):5043–5053Google Scholar
  98. 98.
    Falk J, Bechara A, Fiore R, Nawabi H, Zhou H, Hoyo-Becerra C, Bozon M, Rougon G, Grumet M, Puschel AW, Sanes JR, Castellani V (2005) Dual functional activity of semaphorin 3B is required for positioning the anterior commissure. Neuron 48(1):63–75PubMedGoogle Scholar
  99. 99.
    Kolodkin AL, Matthes DJ, Goodman CS (1993) The semaphorin genes encode a family of transmembrane and secreted growth cone guidance molecules. Cell 75(7):1389–1399PubMedGoogle Scholar
  100. 100.
    Luo Y, Raible D, Raper JA (1993) Collapsin: a protein in brain that induces the collapse and paralysis of neuronal growth cones. Cell 75(2):217–227PubMedGoogle Scholar
  101. 101.
    Huber AB, Kolodkin AL, Ginty DD, Cloutier JF (2003) Signaling at the growth cone: ligand-receptor complexes and the control of axon growth and guidance. Annu Rev Neurosci 26:509–563PubMedGoogle Scholar
  102. 102.
    Kruger RP, Aurandt J, Guan KL (2005) Semaphorins command cells to move. Nat Rev Mol Cell Biol 6(10):789–800PubMedGoogle Scholar
  103. 103.
    Fujisawa H, Ohtsuki T, Takagi S, Tsuji T (1989) An aberrant retinal pathway and visual centers in Xenopus tadpoles share a common cell surface molecule, A5 antigen. Dev Biol 135(2):231–240PubMedGoogle Scholar
  104. 104.
    He Z, Tessier-Lavigne M (1997) Neuropilin is a receptor for the axonal chemorepellent Semaphorin III. Cell 90(4):739–751PubMedGoogle Scholar
  105. 105.
    Kolodkin AL, Levengood DV, Rowe EG, Tai YT, Giger RJ, Ginty DD (1997) Neuropilin is a semaphorin III receptor. Cell 90(4):753–762PubMedGoogle Scholar
  106. 106.
    Satoda M, Takagi S, Ohta K, Hirata T, Fujisawa H (1995) Differential expression of two cell surface proteins, neuropilin and plexin, in Xenopus olfactory axon subclasses. J Neurosci 15(1 Pt 2):942–955PubMedGoogle Scholar
  107. 107.
    Takagi S, Kasuya Y, Shimizu M, Matsuura T, Tsuboi M, Kawakami A, Fujisawa H (1995) Expression of a cell adhesion molecule, neuropilin, in the developing chick nervous system. Dev Biol 170(1):207–222PubMedGoogle Scholar
  108. 108.
    Fujisawa H (2004) Discovery of semaphorin receptors, neuropilin and plexin, and their functions in neural development. J Neurobiol 59(1):24–33PubMedGoogle Scholar
  109. 109.
    Schwarz Q, Ruhrberg C (2010) Neuropilin, you gotta let me know: should I stay or should I go? Cell Adh Migr 4(1):61–66PubMedGoogle Scholar
  110. 110.
    Kameyama T, Murakami Y, Suto F, Kawakami A, Takagi S, Hirata T, Fujisawa H (1996) Identification of plexin family molecules in mice. Biochem Biophys Res Commun 226(2):396–402PubMedGoogle Scholar
  111. 111.
    Ohta K, Takagi S, Asou H, Fujisawa H (1992) Involvement of neuronal cell surface molecule B2 in the formation of retinal plexiform layers. Neuron 9(1):151–161PubMedGoogle Scholar
  112. 112.
    Takahashi T, Fournier A, Nakamura F, Wang LH, Murakami Y, Kalb RG, Fujisawa H, Strittmatter SM (1999) Plexin-neuropilin-1 complexes form functional semaphorin-3A receptors. Cell 99(1):59–69PubMedGoogle Scholar
  113. 113.
    Tamagnone L, Artigiani S, Chen H, He Z, Ming GI, Song H, Chedotal A, Winberg ML, Goodman CS, Poo M, Tessier-Lavigne M, Comoglio PM (1999) Plexins are a large family of receptors for transmembrane, secreted, and GPI-anchored semaphorins in vertebrates. Cell 99(1):71–80PubMedGoogle Scholar
  114. 114.
    Rohm B, Ottemeyer A, Lohrum M, Puschel AW (2000) Plexin/neuropilin complexes mediate repulsion by the axonal guidance signal semaphorin 3A. Mech Dev 93(1–2):95–104PubMedGoogle Scholar
  115. 115.
    Negishi M, Oinuma I, Katoh H (2005) Plexins: axon guidance and signal transduction. Cell Mol Life Sci 62(12):1363–1371PubMedGoogle Scholar
  116. 116.
    Bechara A, Nawabi H, Moret F, Yaron A, Weaver E, Bozon M, Abouzid K, Guan JL, Tessier-Lavigne M, Lemmon V, Castellani V (2008) FAK-MAPK-dependent adhesion disassembly downstream of L1 contributes to semaphorin3A-induced collapse. EMBO J 27(11):1549–1562PubMedGoogle Scholar
  117. 117.
    Parra LM, Zou Y (2010) Sonic hedgehog induces response of commissural axons to Semaphorin repulsion during midline crossing. Nat Neurosci 13(1):29–35PubMedGoogle Scholar
  118. 118.
    Carragher NO, Frame MC (2002) Calpain: a role in cell transformation and migration. Int J Biochem Cell Biol 34(12):1539–1543PubMedGoogle Scholar
  119. 119.
    Wu HY, Lynch DR (2006) Calpain and synaptic function. Mol Neurobiol 33(3):215–236PubMedGoogle Scholar
  120. 120.
    Bai G, Chivatakarn O, Bonanomi D, Lettieri K, Franco L, Xia C, Stein E, Ma L, Lewcock JW, Pfaff SL (2011) Presenilin-dependent receptor processing is required for axon guidance. Cell 144(1):106–118PubMedGoogle Scholar
  121. 121.
    Chow VW, Mattson MP, Wong PC, Gleichmann M (2010) An overview of APP processing enzymes and products. Neuromolecular Med 12(1):1–12PubMedGoogle Scholar
  122. 122.
    Guardia-Laguarta C, Pera M, Lleo A (2010) gamma-Secretase as a therapeutic target in Alzheimer’s disease. Curr Drug Targets 11(4):506–517PubMedGoogle Scholar
  123. 123.
    Jorissen E, De Strooper B (2010) Gamma-secretase and the intramembrane proteolysis of Notch. Curr Top Dev Biol 92:201–230PubMedGoogle Scholar
  124. 124.
    Taniguchi Y, Kim SH, Sisodia SS (2003) Presenilin-dependent “gamma-secretase” processing of deleted in colorectal cancer (DCC). J Biol Chem 278(33):30425–30428PubMedGoogle Scholar
  125. 125.
    Sorimachi H, Hata S, Ono Y (2010) Expanding members and roles of the calpain superfamily and their genetically modified animals. Exp Anim 59(5):549–566PubMedGoogle Scholar

Copyright information

© Springer Basel AG 2011

Authors and Affiliations

  1. 1.F.M. Kirby Neurobiology Center, Children’s Hospital and Department of NeurologyHarvard Medical SchoolBostonUSA
  2. 2.CGMC UMR CNRS 5534University of Lyon, University Claude Bernard Lyon1LyonFrance

Personalised recommendations