Detection and Analysis of Growth Factors Affecting Neural Cells

  • Marston Manthorpe
  • David Muir
  • Brigitte Pettmann
  • Silvio Varon
Part of the Neuromethods book series (NM, volume 23)


Individual cellular behaviors are controlled by extrinsic signals within the environmental milieu. These signals maybe ions, nutrients, hormones, or, pertinent to this review, a collection of proteins generally termed “growth factors.” Growth factors, which may have autocrine, paracrine, or endocrine origins, can be presented to cells in a soluble form from the extracellular fluid, or in an insoluble form from adjacent cells or extracellular matrices. Growth factors operate on cells through specific high-affinity cell-surface receptors that when occupied, produce a series of biochemical reactions that collectively comprise alterations of cell behavior. An important field of research aims to understand how, within tissues, individual and combinations of growth factors control cell behaviors. Most of the present information on growth factors derives from the direct examination of factor influences on cells in culture (Varon et al., 1983; Manthorpe et al., 1989). This chapter will focus on nervous system cells (i.e., neurons and glial cells) and will summarize the ways that in vitro cellular behaviors can be affected by growth regulating factors.


Glial Cell Nerve Growth Factor Glial Fibrillary Acid Protein Schwann Cell Neurite Outgrowth 
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.


  1. 1.
    Adler R., Manthorpe M., and Varon S. (1979) Separation of neurons and nonneuronal cells in monolayer cultures from chick embryo optic lobe. Dev. Biol. 69, 424–435.PubMedCrossRefGoogle Scholar
  2. 2.
    Akers R. M., Mosher D. F., and Lilien J. E. (1981) Promotion of retinal neurite outgrowth by substratum-bound fibronectin. Dev. Biol. 86, 179–188.PubMedCrossRefGoogle Scholar
  3. 3.
    Barbin G., Manthorpe M., and Varon, S. (1984a) Purification of the chick eye ciliary neuronotrophic factor. J. Neurochem. 43, 1468–1478.PubMedCrossRefGoogle Scholar
  4. 4.
    Barbin G., Selak I., Manthorpe M., and Varon, S. (1984b) Use of central neuronal cultures for the detection of neuronotrophic agents. Neuroscience 12, 33–43.PubMedCrossRefGoogle Scholar
  5. 5.
    Barde Y.A., Davies A. M., Johnson J. E., Lindsay R. M., and Thoenen H. (1987) Brain-derived neurotrophic factor. Prog. Brain Res. 71, 185–189.PubMedCrossRefGoogle Scholar
  6. 6.
    Baron van Evercooren A., Kleinman H. K., Ohno S., Marangos P., Schwartz M., Dobois-Dalc M. E. (1982) Nerve growth factor, laminin and fibronectin promote neurite growth in human fetal sensory ganglia cultures. J. Neurosci. 8, 179–194.Google Scholar
  7. 7.
    Benveniste E. N. and Merrill J. E. (1986) Stimulation of oligodendroglial proliferation and maturation by interleukin-2. Nature (Lond.) 321, 610–613.CrossRefGoogle Scholar
  8. 8.
    Besnard F., Perraud F., Sensenbrenner M., and Labourdette G. (1987) Platelet-derived growth factor is a mitogen for glial but not for neuronal rat brain cells in vitro. Neurosci. Lett. 73, 287–292.PubMedCrossRefGoogle Scholar
  9. 9.
    Besnard F., Perraud F., Sensenbrenner M., and Labourdette G. (1989) Effects of acidic and basic fibroblast growth factors on proliferation and maturation of cultured rat oligodendrocytes. Int. J. Dev. Neurosci. 7, 401–409.PubMedCrossRefGoogle Scholar
  10. 10.
    Bixby J. L. and Zhang R. (1990) Purified N-cadherin is a potent substrate for the rapid induction of neurite outgrowth. J. Cell Biol. 110, 1253–1260.PubMedCrossRefGoogle Scholar
  11. 11.
    Bixby J. L., Lillien J., and Reichardt L. F. (1988) Identification of the major proteins that promote neuronal process outgrowth on Schwann cells in vitro. J. Cell Biol. 107, 353–361.PubMedCrossRefGoogle Scholar
  12. 12.
    Bosch E. P., Zhong W., and Lim R. (1989) Axonal signals regulate expression of glia maturation factor-beta in Schwann cells: an immunohisto-chemical study of injured sciatic nerves and cultured Schwann cells. J. Neurosci. 9, 3690–3698.PubMedGoogle Scholar
  13. 13.
    Bottenstein J. E. (1990) Growth requirements in vitro of oligodendrocyte cell lines and neonatal rat brain oligodendrocytes. Proc. Natl. Acad. Sci. USA 83, 1955–1959.CrossRefGoogle Scholar
  14. 14.
    Brockes J. P., Fields K. L., and Raff M. C. (1979) Studies on cultured rat Schwann cells: I. Establishment of purified populations from cultures of peripheral nerve. Brain Res. 165, 105–118.PubMedCrossRefGoogle Scholar
  15. 15.
    Bruckenstein D., Johnson M. I., and Higgins D. (1989) Age-dependent changes in the capacity of rat sympathetic neurons to form dendrites in tissue culture. Brain Res. 46, 21–32.CrossRefGoogle Scholar
  16. 16.
    Buck C. A. and Horwitz A. F. (1987) Integrin, a transmembrane glycoprotein complex mediating cell-substratum adhesion. J. Cell Sci. 8, 231–250.CrossRefGoogle Scholar
  17. 17.
    Bunge R. P., Bunge M. B., and Eldridge C. F. (1986) Linkage between axonal ensheathment and basal lamina production by Schwann cells. Ann. Rev. Neurosci. 9, 305–328.PubMedCrossRefGoogle Scholar
  18. 18.
    Calof A. and Reichardt L. F. (1984) Motoneurons purified by cell sorting respond to two distinct activities in myotube conditioned medium. Dev. Biol. 106, 1541–1549.CrossRefGoogle Scholar
  19. 19.
    Cardwell M. C. and Rome L. H. (1988a) Evidence that an RGD-dependent receptor mediates the binding of oligodendrocytes to a novel ligand in a glial-derived matrix. J. Cell Biol. 107, 1541–1549.PubMedCrossRefGoogle Scholar
  20. 20.
    Cardwell M. C. and Rome L. H. (1988b) RGD-containing peptides inhibit the synthesis of myelin-like membrane by cultured oligodendrocytes. J. Cell Biol. 107, 1551–1559.PubMedCrossRefGoogle Scholar
  21. 21.
    Carnow T. B., Manthorpe M., Davis G. E., and Varon, S. (1985) Localized survival of ciliary ganglionic neurons identifies neuronotrophic factor bands on nitrocellulose blots. J. Neurosci. 5, 1965–1971.PubMedGoogle Scholar
  22. 22.
    Caroni P. and Schwab M. (1988) Two mewmbrane fractions from rat central myelin with inhibitory properties for neurite growth and fibroblast spreading. J. Cell Biol. 106, 1281–1288.PubMedCrossRefGoogle Scholar
  23. 23.
    Cattaneo E. and McKay R. (1990) Proliferation and differentiation of neuronal stem cells regulated by nerve growth factor. Nature (Lend.) 347, 762–765.CrossRefGoogle Scholar
  24. 24.
    Claude P., Parade I. M, Gordon K. A., D’Amore P. A., and Wagner J. A. (1988) Acidic fibroblast growth factor stimulates adrenal chromaffin cells to proliferate and to extend neurites, but is not a long-term survival factor. Neuron 1, 783–790.PubMedCrossRefGoogle Scholar
  25. 25.
    Cohen S., Levi-Montalcini R., and Hamburger V. (1954) A nerve growth-stimulating factor isolated from sarcomas 37 and 180. Proc. Natl. Acad. Sci. USA 40, 1014–1018.PubMedCrossRefGoogle Scholar
  26. 26.
    Davis J. B. and Stroobant P. (1990) Platelet-derived growth factors and fibroblast growth factors are mitogens for rat Schwann cells. J. Cell Biol. 110, 1353–1360.PubMedCrossRefGoogle Scholar
  27. 27.
    Davis G. E., Manthorpe M., and Varon S. (1985a) Parameters of neuritic growth from ciliary ganglion neurons in vitro: Influence of laminin, Schwannoma polyornithine-binding neurite promoting factor and ciliary neuronotrophic factor. Dev. Brain Res. 17, 75–84.CrossRefGoogle Scholar
  28. 28.
    Davis G. E., Manthorpe M., Engvall E., and Varon S. (1985b) Isolation and characterization of rat Schwannoma neurite-promoting factor: Evidence that the factor contains laminin. J. Neurosti. 5, 2662–2671.Google Scholar
  29. 29.
    Davis G. E., Manthorpe M., Williams L. R., and Varon S. (1986). Characterization of a laminin-containing neurite-promoting factor and a neuronotrophic factor from peripheral nerve and related sources. Ann. NY Acad. Sci. 486, 194–205.PubMedCrossRefGoogle Scholar
  30. 30.
    Davis G. E., Klier F. G., Engvall E., Cornbrooks C., Varon S., and Manthorpe M. (1987) Association of laminin with heparan and chondroitin sulfate-bearing proteoglycans in neurite-promoting complexes from rat Schwannoma cells. Neurochem. Res. 12, 909–921.PubMedCrossRefGoogle Scholar
  31. 31.
    Dean D. H., Hiramoto R. N., and Ghanta V. K. (1987) Modulation of immune response. A possible role for murine salivary epidermal and nerve growth factors. J. Periodont. 58, 498–500.PubMedCrossRefGoogle Scholar
  32. 32.
    Dillner L., Dickerson K., Manthorpe M., Ruoslahti E., and Engvall E. (1988) The neurite-promoting domain of human laminin promotes attachment and induces characteristic morphology in non-neuronal cells. Exp. Cell Res. 177, 186–198.PubMedCrossRefGoogle Scholar
  33. 33.
    Drazba J. and Lemmon V. (1990) The role of cell adhesion molecules in neurite outgrowth on Muller cells. Dev. Biol. 138, 82–93.PubMedCrossRefGoogle Scholar
  34. 34.
    Eccelston P. A., Jessen K. R., and Mirsky R. (1989a) Transforming growth factor-beta and gamma-interferon have dual effects on growth of peripheral glia. J. Neurosci. Res. 24, 524–530.CrossRefGoogle Scholar
  35. 35.
    Eccleston P. A., Mirsky R., and Jessen K. R. (1989b) Type I collagen preparations inhibit DNA synthesis in glial cells of the peripheral nervous system. Exp. Cell Res. 182, 173–185.PubMedCrossRefGoogle Scholar
  36. 36.
    Edelman G. M. (1987) Epigentetic rules for expression of cell adhesion molecules during morphogenesis. CIBA Found. Symp. 125, 192–216.PubMedGoogle Scholar
  37. 37.
    Ehrig K., Lievo I., and Engvall E. (1990) Merosin and Laminin; Molecular relationship and role in nerve-muscle development, Ann. NY Acad. Sci. 580, 276–280.PubMedCrossRefGoogle Scholar
  38. 38.
    Engvall E., Davis G. E., Dickerson K., Ruoslahti E., Varon S., and Manthorpe M. (1986) Mapping of domains in human laminin using monoclonal antibodies: localization of the neurite-promoting site. J. Cell Biol. 103, 2457–2465.PubMedCrossRefGoogle Scholar
  39. 39.
    Engvall E., Muir D., and Manthorpe M. (1992) Merosin is possesses cell attachment and neurite promoting activities. Cell Exp. Res., in press.Google Scholar
  40. 40.
    Faivre-Bauman A., Puymirat J., Loudes C., Barret A., and Tixier-Vidal A. (1984) Laminin promotes attachment and neurite elongation of fetal hypothalamic neurons grown in serum free medium. Neurosci. Lett. 44, 83–89.PubMedCrossRefGoogle Scholar
  41. 41.
    Goetschy J. R, Ulrich G., Aunis D., and Ciesielski-Treska J. (1987) Fibronectin and collagens modulate me proliferation and morphology of astroglial cells in culture. Int. J. Dev. Neurosci. 5, 63–70.PubMedCrossRefGoogle Scholar
  42. 42.
    Goretzki P. E., Wahl R. A., Becker R., Koller C., Branscheid D., Grussendorf M., and Roeher H. D. (1987) Nerve growth factor (NGF) sensitizes human medullary thyroid carcinoma (hMTC) cells for cytostatic therapy in vitro. Surgery 102, 1035–1042.PubMedGoogle Scholar
  43. 43.
    Gospodarowicz D., Neufeld G., and Schweigerer L. (1986) Fibroblast Growth Factor. Mol. Cell. Endocrinol. 46, 187–204.PubMedCrossRefGoogle Scholar
  44. 44.
    Greene L. A., Aletta J. M., Rubenstein A., and Green S. H. (1987) PC12 pheochromocytoma cell: culture, nerve growth factor treatment, and experimental exploitation. Methods Enzymol. 147, 207–216.PubMedCrossRefGoogle Scholar
  45. 45.
    Gurwitz D. and Cunningham D. D. (1987) Heparan sulfate proteoglycan and laminin mediate two different types of neurite outgrowth. J Neurosci. 7, 2293–2304.Google Scholar
  46. 46.
    Gurwitz D. and Cunningham D. D. (1988) Thrombin modulates and reverses neuroblastoma neurite outgrowth. Proc. Natl. Acad. Sci. USA 85, 3440–3444.PubMedCrossRefGoogle Scholar
  47. 47.
    Hantaz-Ambroise D., Vigny M., and Koenig J. (1987) Heparan sulfate proteoglycan and laminin mediate two different types of neurite outgrowth. J. Neurosci. 7, 2293–2304.PubMedGoogle Scholar
  48. 48.
    Hayman E. G., Engvall E., A’Hearn E., Barnes D., Pierschbacher M., and Ruoslahti E. (1982) Cell attachment on replicas of SDS polyacrylamide gels reveals two adhesive plasma proteins. J. Cell Biol. 95, 20–23.PubMedCrossRefGoogle Scholar
  49. 49.
    Hughes S. M., Lillien L. E., Raff M. C., Rohrer H., and Sendtner M. (1989) Ciliary neurotrophic factor induces type-2 astrocyte differentiation in culture. Nature (Lond.) 335, 70–73.CrossRefGoogle Scholar
  50. 50.
    Hunter S. F. and Bottenstein J. E. (1990) Growth factor responses of enriched bipotential glial progenitors. Brain Res. 54, 235–248.CrossRefGoogle Scholar
  51. 51.
    Hynes R. O. (1987) Integrins: a family of cell surface receptors. Cell 48, 549–554.PubMedCrossRefGoogle Scholar
  52. 52.
    Juurlink B. H., Munoz D. G., and Devon R. M. (1990) Calcitonin gene-related peptide identifies spinal motoneurons in vitro. J. Neurosci. Res. 26, 238–241.PubMedCrossRefGoogle Scholar
  53. 53.
    Kahan B. W. and Kramp D. C. (1987) Nerve growth factor stimulation of mouse embryonal carcinoma cell migration. Cancer Res. 47, 6324–6328.PubMedGoogle Scholar
  54. 54.
    Kato T., Ito J., and Tanaka R. (1987) Functional dissociation of dual activities of glia maturation factor: inhibition of glial proliferation and preservation of differentiation by glial growth inhibitory factor. Brain Res. 430, 153–156.PubMedGoogle Scholar
  55. 55.
    Kleinman H. K., Cannom F. B., Laurie G. W., Hassell J. R., Aumailley M., Terranova V. P., Martin G. R., and Dubois-Dalcq M. (1985) Biological activities of laminin. J. Cell. Biochem. 27, 317–325.PubMedCrossRefGoogle Scholar
  56. 56.
    Kligman D. (1982) Isolation of a protein from bovine brain which promotes neurite extension from chick embryo cerebral cortex neurons in defined medium. Brain Res. 250, 93–100.PubMedCrossRefGoogle Scholar
  57. 57.
    Lam A., Fuller F., Miller J., Kloss J., Manthorpe M., Varon S., and Cordell B. (1991) Sequence and structural organization of the human gene encoding ciliary neurotrophic factor. Gene, 102, 271–276.PubMedCrossRefGoogle Scholar
  58. 58.
    Lazarovici P., Dickens G., Kuzuya H., and Guroff G. (1987) Long-term, heterologous down-regulation of the epidermal growth factor receptor in PC12 cells by nerve growth factor. J. Cell Biol. 104, 1611–1621.PubMedCrossRefGoogle Scholar
  59. 59.
    Letourneau P. C., Pech I. V., Rogers S. L., Palm S. L., McCarthy J. B., and Furcht L. T. (1988) Growth cone migration across extracellular matrix components depends on integrin, but migration across glioma cells does not. J. Neurosci. Res. 21, 286–297.PubMedCrossRefGoogle Scholar
  60. 60.
    Levi-Montalcini R. (1952) Effects of mouse tumor transplantation on the nervous system. Ann. NY Acad. Sci. 55, 330–343.PubMedCrossRefGoogle Scholar
  61. 61.
    Levi-Montalcini R. (1987) The nerve growth factor 35 years later. Science 237, 1154–1162.PubMedCrossRefGoogle Scholar
  62. 62.
    Lillien L. E., Sendtner M., Rohrer H., Hughes S., and Raff M. C. (1988) Type-2 astrocyte development in rat brain cultures is initiated by a CNTF-like protein produced by type-1 astrocytes. Neuron 1, 485–494.PubMedCrossRefGoogle Scholar
  63. 63.
    Lim R., Hicklin D. J., Ryken T. C, Han X. M., Liu K. N., Miller J. F., and Baggenstoss B. A. (1986) Suppression of glioma growth in vitro and in vivo by glia maturation factor. Cancer Res. 46, 5241–5247.PubMedGoogle Scholar
  64. 64.
    Lim R., Liu Y. X., and Zaheer A. (1990) Glia maturation factor beta regulates the growth of N18 neuroblastoma cells. Dev. Biol. 137, 444–450.PubMedCrossRefGoogle Scholar
  65. 65.
    Longo F. M., Manthorpe M., and Varon S. (1982a) Spinal cord neuronotrophic factors (SCNTFs): I. Bioassay of Schwannoma and other conditioned media. Dev. Brain Res. 3, 277–294.CrossRefGoogle Scholar
  66. 66.
    Longo F. M., Manthorpe M., Skaper S. D., Lundborg G., and Varon S. (1982b) Neuronotrophic activities in fluid accumulated in vivo within silicone nerve regeneration chambers. Brain Res. 261, 109–117.CrossRefGoogle Scholar
  67. 67.
    Longo F. M., Skaper S. D., Manthorpe M., Lundborg G., and Varon S. (1983) Temporal changes, in neuronotrophic activities accumulating in vivo within nerve regeneration chambers. Exp. Neurol. 81, 756–769.PubMedCrossRefGoogle Scholar
  68. 68.
    Longo F. M., Hayman E., Davis G. E., Manthorpe M., Engvall E., Ruoslahti E., and Varon S. (1984a) Neurite promoting factors and extracellular matrix components accumulating in vivo within nerve regeneration chambers. Brain Res. 309, 105–117.PubMedCrossRefGoogle Scholar
  69. 69.
    Longo F. M., Selak I., Zovickian J., Manthorpe M., Varon S., and U. H.-S. (1984b) Neuronotrophic activities in cerebrospinal fluid of head trauma patients. Exp. Neurol. 84, 207–218.PubMedCrossRefGoogle Scholar
  70. 70.
    Louis J.-C., Magal E., Muir D., Varon S., and Manthorpe M. (1992) Rat brain oligodendroglial cell proliferation is inhibited by an autocrine factor, submitted.Google Scholar
  71. 71.
    Ludecke G. and Unsicker K. (1990) Mitogenic effect of neurotrophic factors on human IMR 32 neuroblastoma cells. Cancer 65, 2270–2278.PubMedCrossRefGoogle Scholar
  72. 72.
    Maisonpierre P. C., Bellnisco L., Squinto S., Ip N. Y., Furth M. E., Lindsay R. M., and Yancopoulos G. D. (1990) Neurotrophin-3: A neurotrophic factor related to NGF and BDNF. Science 247, 1446–1451.PubMedCrossRefGoogle Scholar
  73. 73.
    Manthorpe M., Skaper S. D., Adler R., Landa K. B., and Varon S. (1980) Cholin-ergic neuronotrophic factors: IV. Fracu’onation properties of an extract from selected chick embryonic eye tissues. J. Neurochem. 34, 69–75.PubMedCrossRefGoogle Scholar
  74. 74.
    Manthorpe M., Skaper S. D., and Varon S. (1981a) Neuronotrophic factors and their antibodies: In: vitro microassays for titration and screening. Brain Res. 230, 295–306.PubMedCrossRefGoogle Scholar
  75. 75.
    Manthorpe M., Varon S., and Adler R. (1981b) Neurite-promoting factor in conditioned medium from RN22 schwannoma cultures: bioassay, fractionation and other properties. J. Neurochem. 37, 759–767.PubMedCrossRefGoogle Scholar
  76. 76.
    Manthorpe M., Skaper S.D., Barbin G., and Varon S. (1982a) Cholinergic neuronotrophic factors (CNTF’s): VII. Concurrent activities on certain nerve growth factor-responsive neurons. J. Neurochem. 38, 415–421.PubMedCrossRefGoogle Scholar
  77. 77.
    Manthorpe M., Longo F. M., and Varon S. (1982b) Comparative features of spinal neuronotrophic factors in fluids collected in vitro and in vivo. J. Neurosci. Res. 8, 241–250.PubMedCrossRefGoogle Scholar
  78. 78.
    Manthorpe M., Nieto-Sampedro M., Skaper S. D., Barbin G., Longo F. M., Lewis E. R., Cotman C. W., and Varon S. (1983a) Neuronotrophic activity in brain wounds in the developing rat. Correlation with implant survival in the wound cavity. Brain Res. 267, 47–56.PubMedCrossRefGoogle Scholar
  79. 79.
    Manthorpe M., Engvall E., Ruoslahti E., Longo F. M., Davis G. E., and Varon S. (1983b) Laminin promotes neuritic regeneration from cultured peripheral and central neurons. J. Cell Biol. 97, 1882–1890.PubMedCrossRefGoogle Scholar
  80. 80.
    Manthorpe M. and Varon S. (1985) Regulation of neuronal survival and neuritic growth in the avian ciliary ganglion by trophic factors, in Growth and Maturation Factors, vol. 3. (Guroff G., ed.), John Wiley and Sons, New York. pp. 77–117.Google Scholar
  81. 81.
    Manthorpe M., Fagnani R., Skaper S. D., and Varon S. (1986a) An automated colorimetric microassay for neuronotrophic factors. Brain Res. 390, 191–198.PubMedCrossRefGoogle Scholar
  82. 82.
    Manthorpe M., Skaper S. D., Williams L. R., and Varon S. (1986b) Purification of adult rat sciatic nerve ciliary neuronotrophic factor. Brain Res. 367, 282–286.PubMedCrossRefGoogle Scholar
  83. 83.
    Manthorpe M., Rudge J., and Varon S. (1986c) Astroglial contributions to neuronal survival and neuritic growth, in Astrocytes, vol. 2. (Fedoroff S. and Vernadakis A., eds.), Academic Press, New York, pp. 315–376.Google Scholar
  84. 84.
    Manthorpe M., Pettmann B., and Varon S. (1987) Modulation of astroglial cell output of neuronotrophic and neurite promoting factors, in Biochemical Pathology of Astrocytes (Norenberg M. and Schousboe A., eds.), Alan R. Liss, Inc., New York, pp. 41–57.Google Scholar
  85. 85.
    Manthorpe M., Ray J., Pettmann B., and Varon S. (1989) Ciliary neuronotrophic factors, in Nerve Growth Factors (Rush R., ed.), John Wiley & Sons, New York, pp. 31–56.Google Scholar
  86. 86.
    Manthorpe M., Muir D., Hagg T., and Varon S. (1992) Growth promoting and inhibiting factors for neurons, in Advances in Neural Regeneration Research (Seil R, ed.), Alan R. Liss, New York, in press.Google Scholar
  87. 87.
    Martinou J. C., Le Van Thai A., Cassar G., Roubinet R., and Weber M. J. (1989) Characterization of two factors enhancing choline acetyltrans-ferase activity in cultures of purified rat motoneurons. J. Neurosd. 9, 3645–3656.Google Scholar
  88. 88.
    Matsuda H., Coughlin M. D., Bienenstock J., and Denburg J. A. (1988) Nerve growth factor promotes human hemopoietic colony growth and differentiation. Proc. Nat. Acad. Sci. 85, 6508–6512.PubMedCrossRefGoogle Scholar
  89. 89.
    McCarthy K. and DeVellis J. (1980) Preparation of separate astroglial and oligodendroglial cell cultures from rat cerebral tissue. J. Cell Biol. 85, 890–902.PubMedCrossRefGoogle Scholar
  90. 90.
    McMorris F. A. and Dubois-Dalcq M. (1988) Insulin-like growth factor I promotes cell proliferation and oligodendroglial commitment in rat glial progenitor cells developing in vitro. J. Neurosci. Res. 21, 199–209.PubMedCrossRefGoogle Scholar
  91. 91.
    Montz H. P. M., Davis G. E., Skaper S. D., Manthorpe M., and Varon S. (1985) Tumor-promoting phorbol diester mimics two distinct neuronotrophic factors. Dev. Brain Res. 23, 150–154.CrossRefGoogle Scholar
  92. 92.
    Morrison R. S., Kornblum H. I., Leslie F. M., and Bradshaw R. A. (1987) Trophic stimulation of cultured neurons from neonatal rat brain by epidermal growth factor. Science 238, 72–75.PubMedCrossRefGoogle Scholar
  93. 93.
    Morrison R. S., Keating R. R, and Moskal J. R. (1988) Basic fibroblast growth factor and epidermal growth factor exert differential effects on CNS neurons. J. Neurosci. Res. 21, 71–79.PubMedCrossRefGoogle Scholar
  94. 94.
    Mosmann T. (1983) Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J. Immunol. Methods 65, 55–63.PubMedCrossRefGoogle Scholar
  95. 95.
    Muir D., Engvall E., Varon S., and Manthorpe M. (1989a) Schwannoma cell-derived inhibitor of the neurite-promoting activity of laminin. J. Cell Biol. 109, 2353–2362.PubMedCrossRefGoogle Scholar
  96. 96.
    Muir D., Gennrich C, Varon S., and Manthorpe M. (1989b) Rat sciatic nerve Schwann cell microcultures: Responses to mitogens and production of trophic and neurite promoting factors. Neurochem. Res. 14, 1013–1016.CrossRefGoogle Scholar
  97. 97.
    Muir D., Varon S., and Manthorpe M. (1990a) An ELISA for bromodeoxyuridine incorporation using fixed microcultures. Anal. Biochem. 185, 377–382.PubMedCrossRefGoogle Scholar
  98. 98.
    Muir D., Varon S., and Manthorpe M. (1990b) Schwann cell proliferation is under negative autocrine control. J. Cell Biol. 111, 2663–2667.PubMedCrossRefGoogle Scholar
  99. 99.
    Neugebauer K. M., Tomaselli K. J., Lilien J., and Reichardt L. F. (1988) N-cadherin, NCAM, and integrins promote retinal neurite outgrowth on astrocytes in vitro. J. Cell Biol. 107, 1177–1187.PubMedCrossRefGoogle Scholar
  100. 100.
    Otten U., Ehrhard P., and Peck R. (1989) Nerve growth factor induces growth and differentiation of human B lymphocytes. Proc. Nat Acad. Sci. 86, 10059–10063.PubMedCrossRefGoogle Scholar
  101. 101.
    Perraud F., Besnard F., Sensenbrenner M., and Labourdette G. (1987) Thrombin is a potent mitogen for rat astroblasts but not for oligodendroblasts and neuroblasts in primary culture. Int. J. Dev. Neurosci. 5, 181–188.PubMedCrossRefGoogle Scholar
  102. 102.
    Perraud F., Besnard F., Labourdette G., and Sensenbrenner M. (1988a) Proliferation of rat astrocytes, but not of oligodendrocytes, is stimulated in vitro by protease inhibitors. Int. J. Dev. Neurosci. 6, 261–266.PubMedCrossRefGoogle Scholar
  103. 103.
    Perraud F., Besnard F., Pettmann B., Sensenbrenner M., and Labourdette G. (1988b) Effects of acidic and basic fibroblast growth factors (aFGF and bFGF) on the proliferation and the glutamine synthetase expression of rat astroblasts in culture. Glia 1, 124–131.PubMedCrossRefGoogle Scholar
  104. 104.
    Pettmann B., Powell J., Manthorpe M., and Varon S. (1989) Biological activities of Nerve Growth Factor bound to nitrocellulose paper by Western blotting. J. Neurosci. 8, 3524–3632.Google Scholar
  105. 105.
    Pettmann B., Janet T., Labourdette G., Sensenbrenner M., Varon S., and Manthorpe M. (1992) Biologically active basic fibroblast growth factor migrates at 27 kD in “non-denaturing” SDS-polyacrylamide gel electrophoresis. submitted.Google Scholar
  106. 106.
    Pringle N., Collarini E. J., Mosley M. J., Heldin C. H., Westermark B., and Richardson W. D. (1989) PDGF A chain homodimers drive proliferation of bipotential (O-2A) glial progenitor cells in the developing rat optic nerve. Embo J. 8, 1049–1056.PubMedGoogle Scholar
  107. 107.
    Puro D. G., Mano T., Chan C. C., Fukuda M., and Shimada H. (1990) Thrombin stimulates the proliferation of human retinal glial cells. Graefes Arch. Clin. Exp. Ophthalmol. 228, 169–173.PubMedGoogle Scholar
  108. 108.
    Rakowicz-Szulczynska E. M. and Koprowski H. (1989) Antagonistic effect of PDGF and NGF of transcription of ribosomal DNA and tumor cell proliferation. Biochem. Biophys. Res. Commun. 163, 656–694.CrossRefGoogle Scholar
  109. 109.
    Ridley A. J., Davis J. B., Stroobant P., and Land H. (1989) Transforming growth factors-beta 1 and beta 2 are mitogens for rat Schwann cells. J. Cell Biol. 109, 3419–3424.PubMedCrossRefGoogle Scholar
  110. 110.
    Rogers S. L., Letourneau P. C, Palm S. L. and Furcht L. T., (1983) Neurite extension by peripheral and central nervous system neurons in response to substratum-bound fibronectin and laminin. Dev. Biol. 98, 212–220.PubMedCrossRefGoogle Scholar
  111. 111.
    Rogers S. L., Letourneau P. C, Peterson B. A., Furcht L. T., and McCarthy J. B. (1987) Selective interaction of peripheral and central nervous system cells with two distinct cell-binding domains of fibronectin. J. Cell Biol. 105, 1435–1442.PubMedCrossRefGoogle Scholar
  112. 112.
    Rogister B., Leprince P., Bonhomme V., Rigo J. M., Delree P., Colige A., and Moonen G. (1990) Cultured neurons release an inhibitor of astroglia proliferation (astrostatine). J. Neurosci. Res. 25, 58–70.PubMedCrossRefGoogle Scholar
  113. 113.
    Rudge J., Davis G., Manthorpe M., and Varon, S. (1987) An examination of ciliary neuronotrophic factors from avian and rodent tissue extracts using a blot and culture technique. Dev. Brain Res. 32, 103–110.CrossRefGoogle Scholar
  114. 114.
    Rudge J. R., Manthorpe M., and Varon S. (1985) The output of neuronotrophic and neurite-promoting agents from brain astroglial cells: A microculture method for screening potential regulatory molecules. Dev. Brain Res. 19, 161–172.CrossRefGoogle Scholar
  115. 115.
    Rudkin B. B., Lazarovici P., Levi B. Z., Abe Y., Fujita K., and Guroff G. (1989) Cell cycle-specific action of nerve growth factor in PC12 cells: differentiation without proliferation. EMBO J. 8, 3319–3325.PubMedGoogle Scholar
  116. 116.
    Ruoslahti E. and Piersbacher M. D. (1987) New perspectives in cell adhesion: RGD and integrins. Science 328, A91–A97.Google Scholar
  117. 117.
    Rydel R. E. and Greene L. A. (1987) Acidic and basic fibroblast growth factors promote stable neurite outgrowth and neuronal differentiation in cultures of PC12 cells. J. Neurosci. 7, 3639–3653.PubMedGoogle Scholar
  118. 118.
    Saneto R. P., Altman A., Knobler R. L., Johnson H. M., and de Vellis J. (1986) Interleukin 2 mediates the inhibition of oligodendrocyte progenitor cell proliferation in vitro. Proc. Nat. Acad. Sci. 83, 9221–9225.PubMedCrossRefGoogle Scholar
  119. 119.
    Sawada M., Suzamura A., Yamamoto H., and Marunouchi T. (1990) Activation and proliferation of the isolated microglia by colony stimulating factor-1 and possible involvement of protein kinase C. Brain Res. 509, 119–124.PubMedCrossRefGoogle Scholar
  120. 120.
    Schnell L. and Schwab M. (1990) Axonal regeneration in the rat spinal cord produced by an antibody against myelin-associated neurite growth inhibitor. Nature (Lond.) 343, 269–272.CrossRefGoogle Scholar
  121. 121.
    Schubert D., Kimura H., LaCorbiere M., Vaughan J., Karr D., and Fischer W. H. (1990) Activin is a nerve cell survival molecule. Nature (Lond.) 344, 868–870.CrossRefGoogle Scholar
  122. 122.
    Schubert D., LaCorbiere M., and Esch F. (1986) A chick neural retina adhesion and survival molecule is a retinol-binding protein. J. Cell Biol. 102, 2295–2301.PubMedCrossRefGoogle Scholar
  123. 123.
    Schwab M. E. and Caroni P. (1988) Oligodendrocytes and CNS myelin are nonpermissive substrates for neurite growth and fibroblast spreading in vitro. J. Neurosci. 8, 2381–2393.PubMedGoogle Scholar
  124. 124.
    Seilheimer B. and Schachner M. (1988) Studies on adhesion molecules mediating interactions between cells and the PNS indicate a major role for LI in mediating sensory neuron growth on Schwann cells. J. Cell Biol. 107, 341–351.PubMedCrossRefGoogle Scholar
  125. 125.
    Skaper S. D., Facci L., Rudge J., Katoh-Semba R., Manthorpe M., and Varon S. (1986) Morphological modulation of cultured rat brain astroglial cells: antagonism by ganglioside GM1. Dev. Brain Res. 25, 21–31.CrossRefGoogle Scholar
  126. 126.
    Thoenen H., Bandtlow C, Heumann R., Lindholm D., Meyer M., and Rohrer H. (1988) Nerve growth factor: cellular localization and regulation of synthesis. Cell. Molec. Neurobiol. 8, 35–40.PubMedCrossRefGoogle Scholar
  127. 127.
    Thorpe L. W. and Perez-Polo J. R. (1987) The influence of nerve growth factor on the in vitro proliferative response of rat spleen lymphocytes. J. Neurosci. Res. 18, 134–139.PubMedCrossRefGoogle Scholar
  128. 128.
    Tomaselli K. J., Neugebauer K. M., Bixby J. L., Lilien J., Reichardt L. F. (1988) N-cadherin and integrins: two receptor systems mat mediate neuronal process outgrowth on astrocyte surfaces. Neuron 1, 33–43.PubMedCrossRefGoogle Scholar
  129. 129.
    Vahlsing H. L., Varon S., Hagg T., Fass-Holmes B., Dekker A., Manley M., and Manthorpe M. (1989) An improved device for continuous intra-ventricular infusions prevents the introduction of pump-derived toxins and increases the effectiveness NGF treatments. Exp. Neurd. 105, 233–243.CrossRefGoogle Scholar
  130. 130.
    Varon S., Adler R., Manthorpe M., and Skaper S. D. (1983) Culture strategies for trophic and other factors directed to neurons, in Neuroscience Approached Through Cell Culture, vol. 2, (Pfeiffer E., ed.), CRC Press, Boca Raton, FL, pp. 53–77.Google Scholar
  131. 131.
    Varon S., Hagg T., and Manthorpe M. (1992) Nerve Growth Factor, in Encyclopedia of Human Biology, (Dulbecco R., ed.), Academic Press, Orlando, FL, in press.Google Scholar
  132. 132.
    Varon S., Hagg T., and Manthorpe M. (1990) Nerve growth-factor in CNS repair and regeneration, in: Plasticity and Regeneration of the Nervous System. Privat A., Timiras P. S., Giacobini E., Lauder J. M., and Vernadakis A., eds. Plenum, New York, in press.Google Scholar
  133. 133.
    Varon S., Hagg T., and Manthorpe M. (1989) Neuronal growth factors, in Frontiers of Clinical Neuroscience, vol. 6, (Seil F. J., ed.), Alan R. Liss, NY, pp. 101–121.Google Scholar
  134. 134.
    Varon S., Manthorpe M., Davis G. E., Williams L. R., and Skaper S. D. (1988) Growth factors, Adv. Neurol. 47, 493–521.PubMedGoogle Scholar
  135. 135.
    Varon S., Skaper S. D., and Manthorpe M. (1981) Trophic activities for dorsal root and sympathetic ganglionic neurons in media conditioned by Schwann and other peripheral cells. Dev. Brain Res. 1, 73–87.CrossRefGoogle Scholar
  136. 136.
    Varon S., Skaper S. D., Barbin G., Selak I., and Manthorpe M. (1984) Low molecular weight agents support survival of cultured neurons from the central nervous system. J. Neurosci. 4, 654–658.PubMedGoogle Scholar
  137. 137.
    Walicke P., Cowan W. M., Ueno A., Baird A., and Guillemin R. (1986a) Fibroblast growth factor promotes survival of dissociated hippocam-pal neurons and enhances neurite extension, Proc. Natl. Acad. Sci. 83, 3012–3016.PubMedCrossRefGoogle Scholar
  138. 138.
    Walicke P., Varon S., and Manthorpe M. (1986b). Purification of a human red blood cell protein supporting the survival of cultured CNS neurons, and its identification as catalase. J. Neurosci. 6, 1114–1121.PubMedGoogle Scholar
  139. 139.
    Walicke P. A. (1990) Fibroblast growth factor (FGF): A multifunctional growth factor in the CNS, in Advances in Neural Regeneration Research, (Seil F., ed.), Wiley-Liss, Inc. NY, pp. 103–114.Google Scholar
  140. 140.
    Wewer U., Albrechtsen R., Manthorpe M., Varon S., Engvall E., and Ruoslahti E. (1983) Human laminin isolated in a nearly intact, biologically active form from placenta by limited proteolysis. J. Biol. Chem. 258, 12654–12660.PubMedGoogle Scholar
  141. 141.
    Williams L. R., Vahlsing H. L., Lindamood T., Varon S., Gage F. H., and Manthorpe M. (1987). A small-gauge cannula device for continuous infusion of exogenous agents into the brain. Exp. Neurol 95, 743–754.PubMedCrossRefGoogle Scholar
  142. 142.
    Wood P. (1976) Separation of functional Schwann cells and neurons from peripheral nerve tissue. Brain Res. 115, 361–375.PubMedCrossRefGoogle Scholar
  143. 143.
    Yavin E., Gabai A., and Gil S. (1992) Nerve growth factor mediates monosialoganglioside-induced release of fibronectin and Jl/tenascin from C6 glioma cells. 56, in press Google Scholar

Copyright information

© The Humana Press Inc. Totowa, New Jersey 1992

Authors and Affiliations

  • Marston Manthorpe
    • 1
  • David Muir
    • 2
  • Brigitte Pettmann
    • 3
  • Silvio Varon
    • 2
  1. 1.Vical, Inc.San Diego
  2. 2.Department of BiologyUniversity of CaliforniaSan Diego, La Jolla
  3. 3.Center for NeurochemistryStrasbourgFrance

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