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The effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) on axonal elongation and fasciculation

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Summary

Ultrastructural examination of neurons treated with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) confirmed our previous finding that TPA promoted neurite differentiation. At the low concentration of 16 nM TPA, the outgrowth of long neurites was correlated with the increased appearance of membrane-filled varicosities and filopodial extensions along the axons. In contrast, treatment with high concentrations of TPA (160 nM) produced dense outgrowths which were shorter in length and organized as thick fascicles. Increased neurite fasciculation appeared to result from the enhanced side-to-side interactions of neighboring neurites by a neural cell adhesion molecule. Axons within these fascicles were retracted and appeared congested with cytoskeletal and membranous components. Treatment with the antibody to the neural cell adhesion molecule defasciculated the thick outgrowths and permitted further axonal elongation.

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References

  • Benowitz L and Routtenberg A (1987) A membrane phosphoprotein associated with neural development, axonal regeneration, phospholipid metabolism and synaptic plasticity. Trends Neurosci 10:527–532

    Google Scholar 

  • Bottenstein JE, Skaper SP, Varon SS, Sato GH (1980) Selective survival of neurons from chick embryo sensory ganglionic dissociates utilizing serum-free supplemented medium. Exp Cell Res 125:185–190

    Google Scholar 

  • Bray D (1979) Mechanical tension produced by nerve cells in tissue culture. J Cell Sci 37:391–410

    Google Scholar 

  • Bunge M (1973) Fine structure of nerve fibres and growth cones of isolated sympathetic neurons in culture. J Cell Biol 56:713–735

    Google Scholar 

  • Castagna M, Takai Y, Kaibuchi K, Sano K, Kikkawa U, Nishizuka Y (1982) Direct activation of calcium-activated, phospholipid dependent protein kinase by tumor promoting phorbol esters. J Biol Chem 257:7847–7851

    Google Scholar 

  • Diamond L, O'Brien TG and Baird WM (1980) Tumor promoters and the mechanism of tumor promotion. Adv Cancer Res 32:1–74

    Google Scholar 

  • Graham RC and Karnovsky MJ (1966) The early stages of absorption of injected horse-radish peroxidase in the proximal tubules of mouse kidney: ultrastructural cytochemistry by a new technique. J Histochem Cytochem 14:291–302

    Google Scholar 

  • Heath JW, Hill CE and Burnstock G (1974) Axon retraction following guanethidine treatment: studies of sympathetic neurons in tissue culture. J Neurocytol 3:263–276

    Google Scholar 

  • Hinek A, Thyberg J and Fridberg U (1977) Electron microscopic studies on embryonic chick spinal ganglion cells: relationship between microtubules and the Golgi complex. J Neurocytol 6:13–15

    Google Scholar 

  • Hsu L, Natyzak D, Trupin GL (1982) A simple microculture system of neuronal explants. J Tissue Cult Methods 7:143–145

    Google Scholar 

  • Hsu L, Natyzak D and Laskin JD (1984) Effects of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate on neurile outgrowth from chick embryo sensory ganglia. Cancer Res 44:4607–4616

    Google Scholar 

  • Hsu L (1985) Neurite-promoting effects of 12-O-tetradecanoylphorbol-13-acetate on chick embryo neurons. Neurosci Lett 62:283–289

    Google Scholar 

  • Hsu L, Jeng A-Y, Chen KY (1989) Induction of neurite outgrowth from chick embryonic ganglia explants by activators of protein kinase C. Neurosci Lett (in press)

  • Ishii DN (1978) Effects of tumor promoters on the response of cultured embryonic chick ganglia to nerve growth factor. Cancer Res 38:3886–3893

    Google Scholar 

  • Levi-Montalcini R, Caramia F, Luce SA, Angeletti PU (1968) In vitro effects of the nerve growth factor on the fine structure of the sensory nerve cells. Brain Res 8:347–362

    Google Scholar 

  • Masurovsky EB, Peterson ER (1973) Photoreconstituted collagen gel from tissue culture substrates. Exp Cell Res 76:447–448

    Google Scholar 

  • Meiri KF, Pfenninger KH, Willard MB (1986) Growth associated protein, GAP 43 a polypeptide that is induced when neurons extend axons, is a component of growth cones and corresponds to pp 46, a major polypeptide of a subcellular fraction enriched in growth cones. Proc Natl Acad Sci USA 83:3537–3541

    Google Scholar 

  • Nishizuka Y (1984) Turnover of inositol phospholipids and signal transduction. Science 225:1365–1370

    Google Scholar 

  • Pannese E (1974) The histogenesis of the spinal ganglia. Adv Anat Embryol Cell Biol 47:1–91

    Google Scholar 

  • Rutishauser U, Gall WE, Edelman GM (1978) Adhesion among neural cells of the chick embryo. IV. Role of the cell surface molecule CAM in the formation of neurite bundles in cultures of spinal ganglia. J Cell Biol 79:382–393

    Google Scholar 

  • Rutishauser U, Edelman GM (1980) Effects of fasciculation on the outgrowth of neurites from spinal ganglia in culture. J Cell Biol 87:370–378

    Google Scholar 

  • Rutishauser U (1988) The neural cell adhesion molecule (NCAM) as a regulator of cell-cell interactions. Science 240:53–57

    Google Scholar 

  • Skene JHP, Jacobson RD, Snipes GJ, Mcquire GB, Norden JJ and Freeman JA (1986) A protein-induced during nerve growth (GAP 43) is a major component of growth cone membranes. Science 233:783–786

    Google Scholar 

  • Yamada KM, Spooner BS, Wessells NK (1971) Ultrastructure and function of growth cones and axons of cultured nerve cells. J Cell Biol 49:614–635

    Google Scholar 

  • Yamasaki H (1984) Modulation of cell differentiation by tumor promoters. In: Slaga TJ (ed) Mechanism of Tumor Promotion IV. CRC Press, Boca Raton, Florida, pp 1–26

    Google Scholar 

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Hsu, L. The effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) on axonal elongation and fasciculation. Anat Embryol 179, 511–518 (1989). https://doi.org/10.1007/BF00319595

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  • DOI: https://doi.org/10.1007/BF00319595

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