Neuropilin and Class 3 Semaphorins in Nervous System Regeneration

Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 515)


Injury to the mature mammalian central nervous system (CNS) is often accompanied by permanent loss of function of the damaged neural circuits. The failure of injured CNS axons to regenerate is thought to be caused, in part, by neurite outgrowth inhibitory factors expressed in and around the lesion. These include several myelin associated inhibitors, proteoglycans, and tenascin-R. Recent studies have documented the presence of class 3 semaphorins in fibroblast-like meningeal cells present in the core of the neural scar formed following CNS injury. Class 3 semaphorins display neurite growth-inhibitory effects on growing axons during embryonic development. The induction of the expression of class 3 semaphorins in the neural scar and the persistent expression of their receptors, the neuropilins and plexins, by injured CNS neurons suggest that they contribute to the regenerative failure of CNS neurons. Neuropilins are also expressed in the neural scar in a subpopulation of meningeal fibroblast and in neurons in the vicinity of the scar. Semaphorin/neuropilin signaling might therefore also be important for cell migration, angiogenis and neuronal cell death in or around neural scars.


Olfactory Epithelium Olfactory Receptor Neuron Adult Central Nervous System Main Olfactory Bulb Olfactory Axon 
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.


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  1. 1.
    Fu SY, Gordon T. The cellular and molecular basis of peripheral nerve regeneration. Mol Neurobiol 1997;14(1–2):67–116.PubMedCrossRefGoogle Scholar
  2. 2.
    Stichel CC, Muller HW. Experimental strategies to promote axonal regeneration after traumatic central nervous system injury. Prog Neurobiol 1998;56(2):119–48.PubMedCrossRefGoogle Scholar
  3. 3.
    Stoll G, Muller HW. Nerve injury, axonal degeneration and neural regeneration: basic insights. Brain Pathol 1999;9(2):313–25.PubMedCrossRefGoogle Scholar
  4. 4.
    Horner PJ, Gage FH. Regenerating the damaged central nervous system. Nature 2000;407(6807):963–70.PubMedCrossRefGoogle Scholar
  5. 5.
    Fawcett JW, Asher RA. The glial scar and central nervous system repair. Brain Res Bull 1999;49(6):377–91.PubMedCrossRefGoogle Scholar
  6. 6.
    Kolodkin AL, Levengood DV, Rowe EG et al. Neuropilin is a semaphorin III receptor. Cell 1997;90(4):753–62.PubMedCrossRefGoogle Scholar
  7. 7.
    Luo Y, Raible D, Raper JA. Collapsin: a protein in brain that induces the collapse and paralysis of neuronal growth cones. Cell 1993;75(2):217–27.PubMedCrossRefGoogle Scholar
  8. 8.
    Tanelian DL, Barry MA, Johnston SA et al. Semaphorin III can repulse and inhibit adult sensory afferents in vivo. Nat Med 1997;3(12):1398–401.PubMedCrossRefGoogle Scholar
  9. 9.
    Giger RJ, Wolfer DP, De Wit GM et al. Anatomy of rat semaphorin III/collapsin-1 mRNA expression and relationship to developing nerve tracts during neuroembryogenesis..1 Comp Neural 1996;375(3):378–92.CrossRefGoogle Scholar
  10. 10.
    Adams RH, Betz H, Puschel AW. A novel class of murine semaphorins with homology to thrombospondin is differentially expressed during early embryogenesis. Mech Dev 1996;57(1):33–45.PubMedCrossRefGoogle Scholar
  11. 11.
    Livesey FJ, Hunt SP. Netrin and netrin receptor expression in the embryonic mammalian nervous system suggests roles in retinal, striatal, nigral, and cerebellar development. Mol Cell Neurosci 1997;8(6):417–29.PubMedCrossRefGoogle Scholar
  12. 12.
    Mark MD, Lohrum M, Puschel AW. Patterning neuronal connections by chemorepulsion: the semaphorins. Cell Tissue Res 1997;290(2):299–306.PubMedCrossRefGoogle Scholar
  13. 13.
    Mori T, Wanaka A, Taguchi A et al. Differential expressions of the eph family of receptor tyrosine kinase genes (sek, elk, eck) in the developing nervous system of the mouse. Brain Res Mol Brain Res 1995;29(2):325–35.PubMedCrossRefGoogle Scholar
  14. 14.
    Zhang JH, Cerretti DP, Yu T et al. Detection of ligands in regions anatomically connected to neurons expressing the Eph receptor Bsk: potential roles in neuron-target interaction. J Neurosci 1996;16(22):7182–92.PubMedGoogle Scholar
  15. 15.
    Pasterkamp RJ, Anderson PN, Verhaagen J. Peripheral nerve injury fails to induce growth of lesioned ascending dorsal column axons into spinal cord scar tissue expressing the axon repellent Semaphorin3A. Eur J Neurosci 2001;13(3):457–71.PubMedCrossRefGoogle Scholar
  16. 16.
    Pasterkamp RJ, Giger RJ, Ruitenberg MJ et al. Expression of the gene encoding the chemorepellent semaphorin III is induced in the fibroblast component of neural scar tissue formed following injuries of adult but not neonatal CNS. Mol Cell Neurosci 1999;13(2):143–66.PubMedCrossRefGoogle Scholar
  17. 17.
    Miranda JD, White LA, Marcillo AE et al. Induction of Eph B3 after spinal cord injury. Exp Neurol 1999;156(1):218–22.PubMedCrossRefGoogle Scholar
  18. 18.
    Pasterkamp RJ, Giger RJ, Verhaagen J. Regulation of semaphorin III/collapsin-1 gene expression during peripheral nerve regeneration. Exp Neurol 1998;153(2):313–27.PubMedCrossRefGoogle Scholar
  19. 19.
    De Winter F, Pasterkamp RJ, Verhaagen J. Semaphorin 3A is expressed in terminal Schwann cells during postnatal development and regeneration of adult rat neuromuscular junctions. Soc.Neurosci.abstr. 1999;25:241.Google Scholar
  20. 20.
    De Winter F, Pasterkamp RJ, Stam FJ et al. Injury-induced regulation of semaphorin 3A expression in the neuromuscular system. Soc.Neurosci.abstr. 2000 26:579.Google Scholar
  21. 21.
    Reier Pi. Neural tissue grafts and repair of the injured spinal cord. Neuropathol Appl Neurobiol 1985; I 1(2):81–104.CrossRefGoogle Scholar
  22. 22.
    Reier PJ, Houle JD. The glial scar: its bearing on axonal elongation and transplantation approaches to CNS repair. Adv Neurol 1988;47:87–138.PubMedGoogle Scholar
  23. 23.
    Li Y, Raisman G. Sprouts from cut corticospinal axons persist in the presence of astrocytic scarring in long-term lesions of the adult rat spinal cord. Exp Neurol 1995;134(1):102–11.PubMedCrossRefGoogle Scholar
  24. 24.
    Devor M. Neuroplasticity in the sparing or deterioration of function after early olfactory tract lesions. Science 1975;190(4218):998–1000.PubMedCrossRefGoogle Scholar
  25. 25.
    Devor M. Neuroplasticity in the rearrangement of olfactory tract fibers after neonatal transection in hamsters. J Comp Neurol 1976;166(1):49–72.PubMedCrossRefGoogle Scholar
  26. 26.
    Grafe MR. Developmental factors affecting regeneration in the central nervous system: early but not late formed mitral cells reinnervate olfactory cortex after neonatal tract section. J Neurosci 1983;3(3):617–30.PubMedGoogle Scholar
  27. 27.
    Sijbesma H, Leonard CM. Developmental changes in the astrocytic response to lateral olfactory tract section. Anat Rec 1986;215(4):374–82.PubMedCrossRefGoogle Scholar
  28. 28.
    David S, Aguayo AJ. Axonal elongation into peripheral nervous system “bridges” after central nervous system injury in adult rats. Science 1981;214(4523):931–3.PubMedCrossRefGoogle Scholar
  29. 29.
    Aguayo AJ, David S, Bray GM. Influences of the glial environment on the elongation of axons after injury: transplantation studies in adult rodents. J Exp Biol 1981;95:231–40.PubMedGoogle Scholar
  30. 30.
    Richardson PM, Issa VM. Peripheral injury enhances central regeneration of primary sensory neurones. Nature 1984;309(5971):791–3.PubMedCrossRefGoogle Scholar
  31. 31.
    Vidal-Sanz M, Bray GM, Villegas-Perez MP et al. Axonal regeneration and synapse formation in the superior colliculus by retinal ganglion cells in the adult rat. J Neurosci 1987;7(9):2894–909.PubMedGoogle Scholar
  32. 32.
    Ramon-Cueto A, Cordero MI, Santos-Benito FF et al. Functional recovery of paraplegic rats and motor axon regeneration in their spinal cords by olfactory ensheathing glia. Neuron 2000;25(2):425–35.PubMedCrossRefGoogle Scholar
  33. 33.
    Carlstedt T. Dorsal root innervation of spinal cord neurons after dorsal root implantation into the spinal cord of adult rats. Neurosci Lett 1985;55(3):343–8.PubMedCrossRefGoogle Scholar
  34. 34.
    Liuzzi FJ, Lasek RJ. Astrocytes block axonal regeneration in mammals by activating the physiological stop pathway. Science 1987;237(4815):642–5.PubMedCrossRefGoogle Scholar
  35. 35.
    Bignami A, Chi NH, Dahl D. Regenerating dorsal roots and the nerve entry zone: an immunofluorescence study with neurofilament and laminin antisera. Exp Neurol 1984;85(2):426–36.PubMedCrossRefGoogle Scholar
  36. 36.
    Caroni P, Schwab ME. Two membrane protein fractions from rat central myelin with inhibitory properties for neurite growth and fibroblast spreading. J Cell Biol 1988;106(4):1281–8.PubMedCrossRefGoogle Scholar
  37. 37.
    Schnell L, Schwab ME. Axonal regeneration in the rat spinal cord produced by an antibody against myelin-associated neurite growth inhibitors. Nature 1990;343(6255):269–72.PubMedCrossRefGoogle Scholar
  38. 38.
    McKerracher L, David S, Jackson DL et al. Identification of myelin-associated glycoprotein as a major myelin-derived inhibitor of neurite growth. Neuron 1994;13(4):805–11.PubMedCrossRefGoogle Scholar
  39. 39.
    Mukhopadhyay G, Doherty P, Walsh FS et al. A novel role for myelin-associated glycoprotein as an inhibitor of axonal regeneration. Neuron 1994;13(3):757–67.PubMedCrossRefGoogle Scholar
  40. 40.
    Bandtlow CE, Schmidt MF, Hassinger TD et al. Role of intracellular calcium in NI-35evoked collapse of neuronal growth cones. Science 1993;259(5091):80–3.PubMedCrossRefGoogle Scholar
  41. 41.
    Caroni P, Schwab ME. Antibody against myelin-associated inhibitor of neurite growth neutralizes nonpermissive substrate properties of CNS white matter. Neuron 1988;1(1):85–96.PubMedCrossRefGoogle Scholar
  42. 42.
    Tang S, Qiu J, Nikulina E et al. Soluble myelin-associated glycoprotein released from damaged white matter inhibits axonal regeneration. Mol Cell Neurosci 2001;18(3):259–69.PubMedCrossRefGoogle Scholar
  43. 43.
    Cole GJ, McCabe CF. Identification of a developmentally regulated keratan sulfate proteoglycan that inhibits cell adhesion and neurite outgrowth. Neuron 1991;7(6):1007–18.PubMedCrossRefGoogle Scholar
  44. 44.
    McKeon RJ, Hoke A, Silver J. Injury-induced proteoglycans inhibit the potential for lamininmediated axon growth on astrocytic scars. Exp Neurol 1995;136(1):32–43.PubMedCrossRefGoogle Scholar
  45. 45.
    Snow DM, Lemmon V, Canino DA et al. Sulfated proteoglycans in astroglial barriers inhibit neurite outgrowth in vitro. Exp Neurol 1990;109(1): 1–30.CrossRefGoogle Scholar
  46. 46.
    Snow DM, Letourneau PC. Neurite outgrowth on a step gradient of chondroitin sulfate proteoglycan (CS-PG). J Neurobiol 1992;23(3):322–36.PubMedCrossRefGoogle Scholar
  47. 47.
    Ajemian A, Ness R, David S. Tenascin in the injured rat optic nerve and in non-neuronal cells in vitro: potential role in neural repair. J Comp Neurol 1994;340(2):233–42.PubMedCrossRefGoogle Scholar
  48. 48.
    Laywell ED, Dorries U, Bartsch U et al. Enhanced expression of the developmentally regulated extracellular matrix molecule tenascin following adult brain injury. Proc Natl Acad Sci U S A l992;89(7):2634–8.CrossRefGoogle Scholar
  49. 49.
    Laywell ED, Steindler DA. Boundaries and wounds, glia and glycoconjugates. Cellular and molecular analyses of developmental partitions and adult brain lesions. Ann N Y Acad Sci 1991;633:122–41.PubMedCrossRefGoogle Scholar
  50. 50.
    Lips K, Stichel CC, Muller HW. Restricted appearance of tenascin and chondroitin sulphate proteoglycans after transection and sprouting of adult rat postcommissural fomix. J Neurocytol 1995;24(6):449–64.PubMedCrossRefGoogle Scholar
  51. 51.
    Zhang Y, Anderson PN, Campbell G et al. Tenascin-C expression by neurons and glial cells in the rat spinal cord: changes during postnatal development and after dorsal root or sciatic nerve injury. J Neurocytol 1995;24(8):585–601.PubMedCrossRefGoogle Scholar
  52. 52.
    Stichel CC, Muller HW. Regenerative failure in the mammalian CNS. Trends Neurosci 1995;18(3):128; discussion 128–9.PubMedCrossRefGoogle Scholar
  53. 53.
    Pasterkamp RJ, De Winter F, Giger RJ et al. Role for semaphorin III and its receptor neuropilin-1 in neuronal regeneration and scar formation? Prog Brain Res 1998;117:151–70.PubMedCrossRefGoogle Scholar
  54. 54.
    Satoda M, Takagi S, Ohta K et al. Differential expression of two cell surface proteins, neuropilin and plexin, in Xenopus olfactory axon subclasses. J Neurosci 1995;15(1 Pt 2):942–55.Google Scholar
  55. 55.
    He Z, Tessier-Lavigne M. Neuropilin is a receptor for the axonal chemorepellent Semaphorin III. Cell 1997;90(4):739–51.PubMedCrossRefGoogle Scholar
  56. 56.
    Giger RJ, Pasterkamp RJ, Heijnen S et al. Anatomical distribution of the chemorepellent semaphorin III/collapsin- 1 in the adult rat and human brain: predominant expression in structures of the olfactory-hippocampal pathway and the motor system. J Neurosci Res 1998;52(1):27–42.PubMedCrossRefGoogle Scholar
  57. 57.
    Kobayashi H, Koppel AM, Luo Y et al. A role for collapsin-I in olfactory and cranial sensory axon guidance. J Neurosci 1997;17(21):8339–52.PubMedGoogle Scholar
  58. 58.
    Renzi MJ, Wexler TL, Raper JA. Olfactory sensory axons expressing a dominant-negative semaphorin receptor enter the CNS early and overshoot their target. Neuron 2000;28(2):437–47.PubMedCrossRefGoogle Scholar
  59. 59.
    Pasterkamp RJ, De Winter F, Holtmaat AJ et al. Evidence for a role of the chemorepellent semaphorin III and its receptor neuropilin-1 in the regeneration of primary olfactory axons. J Neurosci 1998;18(23):9962–76.PubMedGoogle Scholar
  60. 60.
    Pasterkamp RI, Ruitenberg MJ, Verhaagen J. Semaphorins and their receptors in olfactory axon guidance. Cell Mol Biol (Noisy-le-grand) 1999;45(6):763–79.Google Scholar
  61. 61.
    Schwarting GA, Kostek C, Ahmad N et al. Semaphorin 3A is required for guidance of olfactory axons in mice. J Neurosci 2000;20(20):7691–7.PubMedGoogle Scholar
  62. 62.
    Williams-Hogarth LC, Puche AC, Torrey C et al. Expression of semaphorins in developing and regenerating olfactory epithelium. J Comp Neurol 2000;423(4):565–78.PubMedCrossRefGoogle Scholar
  63. 63.
    Gong Q, Shipley MT. Evidence that pioneer olfactory axons regulate telencephalon cell cycle kinetics to induce the formation of the olfactory bulb. Neuron 1995;14(1):91–101.PubMedCrossRefGoogle Scholar
  64. 64.
    Gong Q, Shipley MT. Expression of cxtracellular matrix molecules and cell surface molecules in the olfactory nerve pathway during early development. J Comp Neurol 1996;366(1):1–14.PubMedCrossRefGoogle Scholar
  65. 65.
    Santacana M, Heredia M, Valverde F. Transient pattern of exuberant projections of olfactory axons during development in the rat. Brain Res Dev Brain Res 1992;70(2):213–22.PubMedCrossRefGoogle Scholar
  66. 66.
    Carr VM, Farbman Al. Ablation of the olfactory bulb up-regulates the rate of neurogenesis and induces precocious cell death in olfactory epithelium. Exp Neurol 1992;115(1):55–9.PubMedCrossRefGoogle Scholar
  67. 67.
    GraziadeiPPLevine RR, Graziadei GA. Regeneration of olfactory axons and synapse formation in the forebrain after bulbectomy in neonatal mice. Proc Natl Acad Sci U S A 1978;75 145230–4.CrossRefGoogle Scholar
  68. 68.
    Goshima Y, Nakamura F, Strittmatter P et al. Coilapsin-induced growth cone collapse mediated by an intracellular protein related to UNC-33. Nature 1995;376(6540):509–14.PubMedCrossRefGoogle Scholar
  69. 69.
    Castellani V, Chedotal A, Schachner M et al. Analysis of the LI-deficient mouse phenotype reveals cross-talk between Sema3A and LI signaling pathways in axonal guidance. Neuron 2000;27(2):237–49.PubMedCrossRefGoogle Scholar
  70. 70.
    Doucette JR, Kiernan JA, Flumerfelt BA. The re-innervation of olfactory glomeruli following transection of primary olfactory axons in the central or peripheral nervous system. J Anat I983;137(Pt 1):1–19.Google Scholar
  71. 71.
    Graziadei GA, Graziadei PP. Neurogenesis and neuron regeneration in the olfactory system of mammals. II. Degeneration and reconstitution of the olfactory sensory neurons after axotomy. J Neurocytol 1979;8(2):197–213.PubMedCrossRefGoogle Scholar
  72. 72.
    Graziadei PP, Graziadei GA. Neurogenesis and neuron regeneration in the olfactory system of mammals. I. Morphological aspects of differentiation and structural organization of the olfactory sensory neurons. I Neurocytol 1979;8(1):1–18.CrossRefGoogle Scholar
  73. 73.
    Schwartz Levey M, Chikaraishi DM, Kauer JS. Characterization of potential precursor populations in the mouse olfactory epithelium using immunocytochemistry and autoradiography. J Neurosci 1991;11(11):3556–64.PubMedGoogle Scholar
  74. 74.
    Monti Graziadei GA. Experimental studies on the olfactory marker protein. III. The olfactory marker protein in the olfactory neuroepithelium lacking connections with the forebrain. Brain Res 1983;262(2):303–8.PubMedCrossRefGoogle Scholar
  75. 75.
    Hendricks KR, Kott JN, Lee ME et al. Recovery of olfactory behavior. I. Recovery after a complete olfactory bulb lesion correlates with patterns of olfactory nerve penetration. Brain Res 1994;648(1):121–33.PubMedCrossRefGoogle Scholar
  76. 76.
    Verhaagen J, Zhang Y, Hamers FP et al. Elevated expression of B-50 (GAP-43)-mRNA in a subpopulation of olfactory bulb mitral cells following axotomy. J Neurosci Res 1993;35(2):162–9.PubMedCrossRefGoogle Scholar
  77. 77.
    Berry M, Maxwell WL, Logan A et al. Deposition of scar tissue in the central nervous system. Acta Neurochir Suppl 1983;32:31–53.Google Scholar
  78. 78.
    De Winter F, Oudega M, Lankhorst AJ et al. Injury induced regulation of class 3 semaphorin expression in the rat spinal cord. Exp Neurol 2002;in press.Google Scholar
  79. 79.
    Miyazaki N, Furuyama T, Amasaki M et al. Mouse semaphorin H inhibits neurite outgrowth from sensory neurons. Neurosci Res 1999;33(4):269–74.PubMedCrossRefGoogle Scholar
  80. 80.
    Polleux F, Giger RJ, Ginty DD et al. Patterning of cortical efferent projections by semaphorinneuropilin interactions. Science 1998;282(5395):1904–6.PubMedCrossRefGoogle Scholar
  81. 81.
    Polleux F, Morrow T, Ghosh A. Semaphorin 3A is a chemoattractant for cortical apical dendrites. Nature 2000;404(6778):567–73.PubMedCrossRefGoogle Scholar
  82. 82.
    Skold M, Cullheim S, Hammarberg H et al. Induction of VEGF and VEGF receptors in the spinal cord after mechanical spinal injury and prostaglandin administration. Eur J Neurosci 2000; 12(10):3675–86.PubMedCrossRefGoogle Scholar
  83. 83.
    Soker S, Takashima S, Miao HQ et al. Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor. Cell 1998;92(6):735–45.PubMedCrossRefGoogle Scholar
  84. 84.
    Bartholdi D, Rubin BP, Schwab ME. VEGF mRNA induction correlates with changes in the vascular architecture upon spinal cord damage in the rat. Eur J Neurosci 1997;9(12):2549–60.PubMedCrossRefGoogle Scholar
  85. 85.
    Miao HQ, Soker S, Feiner L et al. Neuropilin-1 mediates collapsin-1/semaphorin III inhibition of endothelial cell motility: functional competition of collapsin-1 and vascular endothelial growth factor-I65, J Cell Biol 1999;146(1):233–42.PubMedCrossRefGoogle Scholar
  86. 86.
    Bagnard D, Vaillant C, Khuth ST et al. Semaphorin 3A-vascular endothelial growth factor-165 balance mediates migration and apoptosis of neural progenitor cells by the recruitment of shared receptor. J Neurosci 2001;21(10):3332–41.PubMedGoogle Scholar
  87. 87.
    Eickholt BJ, Mackenzie SL, Graham A et al. Evidence for collapsin-1 functioning in the control of neural crest migration in both trunk and hindbrain regions. Development 1999;126(10):2181–9.PubMedGoogle Scholar
  88. 88.
    Feiner L, Webber AL, Brown CB et al. Targeted disruption of semaphorin 3C leads to persistent truncus arteriosus and aortic arch interruption. Development 2001;128(16):3061–70.PubMedGoogle Scholar
  89. 89.
    Christensen CR, Klingelhofer J, Tarabykina S et al. Transcription of a novel mouse semaphorin gene, M-semaH, correlates with the metastatic ability of mouse tumor cell lines. Cancer Res 1998;58(6):1238–44.PubMedGoogle Scholar
  90. 90.
    Yamada T, Endo R, Gotoh M et al. Identification of semaphorin E as a non-MDR drug resistance gene of human cancers. Proc Natl Acad Sci U S A 1997;94(26):14713–8.PubMedCrossRefGoogle Scholar
  91. 91.
    Martin-Satue M, Blanco J. Identification of semaphorin E gene expression in metastatic human lung adenocarcinoma cells by mRNA differential display. J Surg Oncol 1999;72(1):18–23.PubMedCrossRefGoogle Scholar
  92. 92.
    Brambilla E, Constantin B, Drabkin H et al. Semaphorin SEMA3F localization in malignant human lung and cell lines: A suggested role in cell adhesion and cell migration. Am J Pathol 2000;156(3):939–50.PubMedCrossRefGoogle Scholar
  93. 93.
    Li M, Shibata A, Li C et al. Myelin-associated glycoprotein inhibits neurite/axon growth and causes growth cone collapse. J Neurosci Res 1996;46(4):404–14.PubMedCrossRefGoogle Scholar
  94. 94.
    Kitsukawa T, Shimono A, Kawakami A et al. Overexpression of a membrane protein, neuropilin, in chimeric mice causes anomalies in the cardiovascular system, nervous system and limbs. Development 1995;121(12):4309–18.PubMedGoogle Scholar
  95. 95.
    Kawasaki T, Kitsukawa T, Bekku Y et al. A requirement for neuropilin-1 in embryonic vessel formation. Development 1999;126(21):4895–902.PubMedGoogle Scholar
  96. 96.
    Behar 0, Golden JA, Mashimo H et al. Semaphorin III is needed for normal patterning and growth of nerves, bones and heart. Nature 1996;383(6600):525–8.PubMedCrossRefGoogle Scholar
  97. 97.
    Beggs JL, Waggener JD. Microvascular regeneration following spinal cord injury: the growth sequence and permeability properties of new vessels. Adv Neurol 1979;22:191–206.PubMedGoogle Scholar
  98. 98.
    Imperato-Kalmar EL, McKinney RA, Schnell L et al. Local changes in vascular architecture following partial spinal cord lesion in the rat. Exp Neurol 1997;145(2 Pt 1):322–8.PubMedCrossRefGoogle Scholar
  99. 99.
    Zhang ZG, Tsang W, Zhang L et al. Up-regulation of neuropilin-I in neovasculature after focal cerebral ischemia in the adult rat. J Cereb Blood Flow Metab 2001;21(5):541–9.PubMedCrossRefGoogle Scholar
  100. 100.
    Amar AP, Levy ML. Pathogenesis and pharmacological strategies for mitigating secondary damage in acute spinal cord injury. Neurosurgery 1999;44(5):1027–39; discussion 1039–40.PubMedCrossRefGoogle Scholar
  101. 101.
    Crowe MJ, Bresnahan JC, Shuman SL et al. Apoptosis and delayed degeneration after spinal cord injury in rats and monkeys. Nat Med 1997;3(1):73–6.PubMedCrossRefGoogle Scholar
  102. 102.
    Shit-van A, Ziv I, Fleminger G et al. Semaphorins as mediators of neuronal apoptosis. J Neurochem 1999;73(3):961–71.Google Scholar
  103. 103.
    Gagliardini V, Fankhauser C. Semaphorin III can induce death in sensory neurons. Mol Cell Neurosci 1999;14(4–5):301–16.PubMedCrossRefGoogle Scholar
  104. 104.
    Fujita H, Zhang B, Sato K et al. Expressions of neuropilin-1, neuropilin-2 and semaphorin 3A mRNA in the rat brain after middle cerebral artery occlusion. Brain Res 2001;914(1–2):1–14.PubMedCrossRefGoogle Scholar
  105. 105.
    Chedotal A, Del Rio JA, Ruiz M et al. Semaphorins III and IV repel hippocampal axons via two distinct receptors. Development 1998;125(21):4313–23.Google Scholar
  106. 106.
    Pozas E, Pascual M, Nguyen Ba-Charvet KT et al. Age-dependent effects of secreted Semaphorins 3A, 3F, and 3E on developing hippocampal axons: in vitro effects and phenotype of Semaphorin 3A (-/-) mice. Mol Cell Neurosci 2001;18(1):26–43.PubMedCrossRefGoogle Scholar
  107. 107.
    Steup A, Ninnemann 0, Savaskan NE et al. Semaphorin D acts as a repulsive factor for entorhinal and hippocampal neurons. Eur J Neurosci 1999;11(2):729–34.PubMedCrossRefGoogle Scholar
  108. 108.
    Taniguchi M, Yuasa S, Fujisawa H et al. Disruption of semaphorin III/D gene causes severe abnormality in peripheral nerve projection. Neuron 1997;19(3):519–30.PubMedCrossRefGoogle Scholar
  109. 109.
    Giger RJ, Cloutier JF, Sahay A et al. Neuropilin-2 is required in vivo for selective axon guidance responses to secreted semaphorins. Neuron 2000;25(1):29–41.PubMedCrossRefGoogle Scholar
  110. 110.
    Chen H, Bagri A, Zupicich JA et al. Neuropilin-2 regulates the development of selective cranial and sensory nerves and hippocampal mossy fiber projections. Neuron 2000;25(1):43–56.PubMedCrossRefGoogle Scholar
  111. 111.
    Holtmaat AJ, Gorter JA, De Wit J et al. Transient downregulation of Semaphorin(D)III/ Collapsin-I expression in a rat model for temporal lobe epilepsy. Axon guidance & Neural plasticity, Cold Spring Harbor 1998:84.Google Scholar
  112. 112.
    Barnes GN, Luo Y, Ebens A et al. Anatomical and temporal specific patterns of semaphorin gene expression in rat brain after kainic acid induced status epilepticus. Soc Neurosci Abstr 1999;25:1793.Google Scholar
  113. 113.
    Barnes GN, Luo Y, McNamara JO. Parallel regulation of Sema3C and Sema3C receptor expression in CAI pyramidal cell layer of rat hippocampus after kainic acid induced status epilepticus. Soc Neurosci Abstr 2000;26:575.Google Scholar
  114. 114.
    Benowitz LI, Rodriguez WR, Neve RL. The pattern of GAP-43 immunostaining changes in the rat hippocampal formation during reactive synaptogenesis. Brain Res Mol Brain Res 1990;8(1):17–23.PubMedCrossRefGoogle Scholar
  115. 115.
    Cremer H, Chazal G, Goridis C et al. NCAM is essential for axonal growth and fasciculation in the hippocampus. Mol Cell Neurosci 1997;8(5):323–35.PubMedCrossRefGoogle Scholar
  116. 116.
    Bendotti C, Vezzani A, Tarizzo G et al. Increased expression of GAP-43, somatostatin and neuropeptide Y mRNA in the hippocampus during development of hippocampal kindling in rats. Eur J Neurosci 1993;5(10):1312–20.PubMedCrossRefGoogle Scholar
  117. 117.
    Meberg PJ, Gall CM, Routtenberg A. Induction of F 1/GAP-43 gene expression in hippocampal granule cells after seizures [corrected]. Brain Res Mol Brain Res 1993;17(3–4):295–9.PubMedCrossRefGoogle Scholar
  118. 118.
    Giger RJ, Pasterkamp RJ, Holtmaat AJ et al. Semaphorin HI: role in neuronal development and structural plasticity. Prog Brain Res 1998;117:133–49.PubMedCrossRefGoogle Scholar
  119. 119.
    Skene JH. Growth-associated proteins and the curious dichotomies of nerve regeneration. Cell 1984;37(3):697–700.PubMedCrossRefGoogle Scholar
  120. 120.
    Skene JH, Virag I. Posttranslational membrane attachment and dynamic fatty acylation of a neuronal growth cone protein, GAP-43. J Cell Biol I989;108(2):613–24.CrossRefGoogle Scholar
  121. 121.
    Brown MC, Perry VH, Hunt SP et al. Further studies on motor and sensory nerve regeneration in mice with delayed Wallerian degeneration. Eur J Neurosci 1994;6(3):420–8.PubMedCrossRefGoogle Scholar
  122. 122.
    Tona A, Perides G, Rahemtulla F et al. Extracellular matrix in regenerating rat sciatic nerve: a comparative study on the localization of laminin, hyaluronic acid, and chondroitin sulfate proteoglycans, including versican. J Histochem Cytochem 1993;41(4):593–9.PubMedCrossRefGoogle Scholar
  123. 123.
    Heumann R, Lindholm D, Bandtlow C et al. Differential regulation of mRNA encoding nerve growth factor and its receptor in rat sciatic nerve during development, degeneration, and regeneration: role of macrophages. Proc Natl Acad Sci U S A 1987;84(23):8735–9.PubMedCrossRefGoogle Scholar
  124. 124.
    Meyer M, Matsuoka I, Wetmore C et al. Enhanced synthesis of brain-derived neurotrophic factor in the lesioned peripheral nerve: different mechanisms are responsible for the regulation of BDNF and NGF mRNA. J Cell Biol 1992;119(1):45–54.PubMedCrossRefGoogle Scholar
  125. 125.
    Gai WP, Zhou XF, Rush RA. Analysis of low affinity neurotrophin receptor (p75) expression in glia of the CNS-PNS transition zone following dorsal root transection. Neuropathol Appl Neurobiol 1996;22(5):434–9.PubMedCrossRefGoogle Scholar
  126. 126.
    Gorio A, Vergani L, Ferro L et al. Glycosaminoglycans in nerve injury: II. Effects on transganglionic degeneration and on the expression of neurotrophic factors. J Neurosci Res 1996;46(5):572–80.PubMedCrossRefGoogle Scholar
  127. 127.
    Benowitz LI, Routtenberg A. GAP-43: an intrinsic determinant of neuronal development and plasticity. Trends Neurosci 1997;20(2):84–91.PubMedCrossRefGoogle Scholar
  128. 128.
    Bisby MA, Tetzlaff W. Changes in cytoskeletal protein synthesis following axon injury and during axon regeneration. Mol Neurobiol I992;6(2–3):107–23.CrossRefGoogle Scholar
  129. 129.
    Jenkins R, McMahon SB, Bond AB et al. Expression of c-Jun as a response to dorsal root and peripheral nerve section in damaged and adjacent intact primary sensory neurons in the rat. Eur J Neurosci 1993;5(6):751–9.PubMedCrossRefGoogle Scholar
  130. 130.
    Robinson GA. Immediate early gene expression in axotomized and regenerating retinal ganglion cells of the adult rat. Brain Res Mol Brain Res 1994;24(1–4):43–54.PubMedCrossRefGoogle Scholar
  131. 131.
    Herdegen T, Blume A, Buschmann T et al. Expression of activating transcription factor-2, serum response factor and cAMP/Ca response element binding protein in the adult rat brain following generalized seizures, nerve fibre lesion and ultraviolet irradiation. Neuroscience 1997;81(I):199–212.PubMedCrossRefGoogle Scholar
  132. 132.
    Gavazzi I, Stonehouse J, Sandvig A et al. Peripheral, but not central, axotomy induces neuropilin-1 mRNA expression in adult large diameter primary sensory neurons. J Comp Neurol 2000;423(3):492–9.PubMedCrossRefGoogle Scholar
  133. 133.
    Shepherd I, Luo Y, Raper JA et al. The distribution of collapsin-1 mRNA in the developing chick nervous system. Dev Biol 1996;173(1):185–99.PubMedCrossRefGoogle Scholar
  134. 134.
    Varela-Echavarria A, Tucker A, Puschel AW et al. Motor axon subpopulations respond differentially to the chemorepellents netrin-1 and semaphorin D. Neuron 1997;18(2):193–207.PubMedCrossRefGoogle Scholar
  135. 135.
    Hornberger MR, Dutting D, Ciossek T et al. Modulation of EphA receptor function by coexpressed ephrinA ligands on retinal ganglion cell axons. Neuron 1999;22(4):731–42.PubMedCrossRefGoogle Scholar
  136. 136.
    Woolf CJ, Shortland P, Coggeshall RE. Peripheral nerve injury triggers central sprouting of myelinated afferents. Nature 1992;355(6355):75–8.Google Scholar
  137. 137.
    Messersmith EK, Leonardo ED, Shatz CJ et al. Semaphorin III can function as a selective chemorepellent to pattern sensory projections in the spinal cord. Neuron 1995;14(5):949–59.PubMedCrossRefGoogle Scholar
  138. 138.
    Puschel AW, Adams RH, Betz H. The sensory innervation of the mouse spinal cord may be patterned by differential expression of and differential responsiveness to semaphorins. Mol Cell Neurosci 1996;7(5):419–31.PubMedCrossRefGoogle Scholar
  139. 139.
    Pasterkamp RJ, Giger RJ, Baker RE et al. Ectopic adenoviral vector-directed expression of Sema3A in organotypic spinal cord explants inhibits growth of primary sensory afferents. Dev Biol 2000;220(2):129–41.PubMedCrossRefGoogle Scholar
  140. 140.
    Reza JN, Gavazzi I, Cohen J. Neuropilin-1 is expressed on adult mammalian dorsal root ganglion neurons and mediates semaphorin3a/collapsin-l-induced growth cone collapse by small diameter sensory afferents. Mol Cell Neurosci 1999;14(4–5):317–26.PubMedCrossRefGoogle Scholar
  141. 141.
    Song HJ, Ming GL, Poo MM. cAMP-induced switching in turning direction of nerve growth cones. Nature 1997;388(6639):275–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  1. 1.Netherlands Institute for Brain ResearchAmsterdamThe Netherlands

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