Turning of nerve growth cones induced by neurotransmitters

Abstract

PATHFINDING by growing nerve processes in the developing nervous system depends on the turning response of the growing tip, the growth cone, to extracellular guidance cues1–4. There is evidence in vivo and in cell culture that some growth cones exhibit chemotropic behaviour5–12, but the identity of endogenous chemoattractants remains elusive. Neurotransmitters appear early in the developing embryo and may have morphogenic roles in development13,14. In cell culture a number of neurotransmitters were found to induce growth inhibition or retraction of neurites15–19. Here we report positive turning responses of the nerve growth cone in a defined extracellular gradient of the neurotransmitter acetylcholine (ACh). The growth cone response depends on the activation of neuronal nicotinic ACh receptors, requires the presence of extracellular Ca2+, and appears to be mediated by Ca2+-calmodulin-dependent protein kinase II. Fluorescence imaging of cytosolic Ca2+ concentration ([Ca2+]i) at the growth cone showed a small but significant evaluation of [Ca2+]i within minutes of the onset of ACh application and before the turning of the growth cone. These findings suggest that neurotransmitters may serve as specific chemoattractants for growth cone guidance and that cytosolic Ca2+ may act as a second messenger in the cytoplasm of the growth cone to initiate the turning response.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1

    Purves, D. & Lichtman, J. W. Principles of Neural Development (Sinauer, Sunderland, MA, 1985).

  2. 2

    Letourneau, P. in Molecular Bases of Neural Development (eds Edelman, G. M., Gall, W. E. & Cowan, W. M.) 269–293 (Wiley, New York, 1985),

  3. 3

    Landmesser, L. Trends Neurosci. 9, 489–491 (1986).

  4. 4

    Bray, D. & Hollenbeck, P. J. A. Rev. Cell Biol. 4, 43–61 (1988).

  5. 5

    Letourneau, P. C. Devel Biol. 66, 183–196 (1978).

  6. 6

    Gunderson, R. & Barret, J. N. Science 206, 1079–1080 (1979).

  7. 7

    Lumsden, A. G. S. & Davis, A. M. Nature 306, 786–788 (1983).

  8. 8

    Tessier-Lavigne, M., Placzek, M., Lumsden, A. G. S., Dodd, J. & Jessel, T. M. Nature 336, 775–778 (1988).

  9. 9

    Menesini-Chen, M. G., Chen, J. S. & Levi-Montalcini, R. Arch. Ital. Biol. 116, 53–84 (1978).

  10. 10

    Jeffner, C. D., Lumsden, A. G. S. & O'Leary, D. D. M. Science 247, 217–220 (1990).

  11. 11

    McCraig, C. D. J. Physiol. 375, 39–54 (1986).

  12. 12

    Yaginuma, H. & Oppenheim, R. W. J. Neurosci. 11, 2598–2613 (1991).

  13. 13

    Buznikov, G. A., Chudakova, I. V., Berysheva, L. V. & Vyazmina, N. M. J. Embryol. exp. Morph. 20, 119–128 (1968).

  14. 14

    Lauder, J. M. Prog. Brain Res. 73, 365–387 (1988).

  15. 15

    Haydon, P. G., McCobb, D. P. & Kater, S. B. Science 226, 561–564 (1984).

  16. 16

    McCobb, D. P., Haydon, P. G. & Kater, S. B. J. Neurosci. Res. 19, 19–26 (1988).

  17. 17

    Lankford, K. L., DeMello, F. G. & Klein, W. L. Proc. natn. Acad. Sci. U.S.A. 85, 2839–2843 (1988).

  18. 18

    Mattson, M. P., Dou, P. & Kater, S. B. J. Neurosci. 8, 2087–2100 (1988).

  19. 19

    Lipton, S. A., Forsch, M. P., Pillips, M. D., Tauck, D. L. & Aizenmann, E. Science 239, 1293–1296 (1988).

  20. 20

    Lohof, A. M., Quillan, M., Dan, Y. & Poo, M-m. J. Neurosci. 12, 1253–1261 (1992).

  21. 21

    Xie, Z. P. & Poo, M-m. Proc. natn. Acad. Sci. U.S.A. 83, 7069–7073 (1986).

  22. 22

    Evers, J., Laser, M., Sun, Y., Xie, Z. P. & Poo, M-m. J. Neurosci. 9, 1523–1539 (1989).

  23. 23

    Patel, N. & Poo, M-m. J. Neurosci. 4, 2939–2947 (1984).

  24. 24

    Mattson, M. P. & Kater, S. B. J. Neurosci. 7, 4034–4043 (1987).

  25. 25

    Rehder, V. & Kater, S. B. J. Neurosci. 12, 3175–3186 (1992).

  26. 26

    Davenport, R. W. & Kater, S. B. Neuron 9, 405–416 (1992).

  27. 27

    Bedlack, R. S. Jr, Wei, M.-d. & Loew, L. M. Neuron 9, 393–403 (1992).

  28. 28

    Vernino, S., Amador, M., Luetje, C. W., Patrick J. & Dani, J. A. Neuron 8, 127–134 (1992).

  29. 29

    Vijayaraghavan, S., Pugh, P. C., Zhang, Z. W., Rathouz, M. M. & Berg, D. K. Neuron 8, 353–362 (1992).

  30. 30

    Bixby, J. L. & Spitzer, N. C. Devl Biol. 106, 89–96 (1984).

  31. 31

    Tokumitsu, H. et al. J. biol. Chem. 265, 4315–4320 (1990).

  32. 32

    Ito, I., Hidaka, H. & Sugiyama, H. Neurosci. Lett. 121, 119–121 (1991).

  33. 33

    Grynkiewicz, G., Poenie, M. & Tsien, R. Y. J. biol. Chem. 260, 3440–3450 (1985).

  34. 34

    Connor, J. A. Cell Calcium 14, 173–188 (1993).

  35. 35

    Connor, J. A. & Nikolakopoulou, G. Lec. Math. Life Sci. 15, 79–101 (1982).

  36. 36

    Cohan, C. S., Connor, J. A. & Kater, S. B. J. Neurosci. 7, 3588–3599 (1987).

  37. 37

    McCobb, D. P., Cohan, C. S., Connor, J. A. & Kater, S. B. Neuron 1, 377–385 (1988).

  38. 38

    Spitzer, C. C. & Lamborghini, H. E. Proc. natn. Acad. Sci. U.S.A. 73, 1641–1645 (1976).

  39. 39

    Anderson, M. J., Cohen, M. W. & Zorychta, E. J. Physiol., Lond. 268, 731–758 (1977).

  40. 40

    Tabti, N. & Poo, M-m. in Culturing Nerve Cells (eds Banker, G. & Goslin, K.) 137–153 (MIT Press, Cambridge, 1991).

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Zheng, J., Felder, M., Connor, J. et al. Turning of nerve growth cones induced by neurotransmitters. Nature 368, 140–144 (1994). https://doi.org/10.1038/368140a0

Download citation

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.