Abstract
Establishment of appropriate neuronal connections during development and regeneration requires the extension of processes that must then grow in the correct direction, find and recognize their targets, and make synapses with them. During development, embryonic neurons gradually establish central and peripheral connections in an evolving cellular environment in which neurotrophic factors are provided by supporting and target cells that promote neuronal survival, differentiation, and process outgrowth. Some cells also release neurotropic factors that direct the outgrowth of neuronal processes toward their targets. Following development the neurotrophic requirements of some adult neurons change so that, although they respond to neurotrophic factors, they no longer require exogenous neurotrophins to survive or to extend processes. Within the central nervous system (CNS), the ability of neurons to extend processes is eventually lost because of a change in their cellular environment from outgrowth permissive to inhibitory. Thus, neuronal connections that are lost in the adult CNS are rarely reestablished. In contrast, the environment of the adult peripheral nervous system fosters process outgrowth and synapse formation. This article discusses the neurotrophic requirements of embryonic and adult neurons, as well as the importance of neurotropic factors in directing the outgrowth of regenerating adult axons.
Similar content being viewed by others
References
Richardson P. M., McGuinness U. M., and Aguayo A. J. (1980)Nature (Lond.) 284, 264.
Weinberg E. L. and Raine C. S. (1980)Brain Res. 198, 1.
Benfey A. J. and Aguayo A. J. (1982)Nature (Lond.) 296, 150.
Schwab M. E. and Caroni P. (1988)J. Neurosci. 8, 2381.
Caroni P. and Schwab M. E. (1988)J. Cell Biol. 106, 1281.
Caroni P. and Schwab M. E. (1988)Neuron 1, 85.
Schnell L. and Schwab M. E. (1990)Nature 343, 269.
Cadelli D. S., Bandtlow C. E., and Schwab M. E. (1992)Exp. Neurol. 115, 189.
Barde Y.-A. (1989)Neuron 2, 1525.
Levi-Montalcini R. (1987)EMBO J. 6, 1145.
Thoenen H. (1991)Trends Neurosci. 14, 165.
Thoenen H. and Barde Y.-A. (1980)Physiol. Rev. 60, 1284.
Johnson E. M., Gorin P. D., Bradeis L. D., and Pearson J. (1980)Science 210, 916.
Hamburger V., Brunso-Bechtold J. K., and Jip J. W. (1981)J. Neurosci. 1, 60.
Johnson J. E., Rich K. M., and Yip H. K. (1986)Trends Neurosci. 9, 33.
Richardson P. M. and Ebendal T. (1982)Brain Res. 246, 57.
Skene J. H. P. and Shooter E. M. (1983)Proc. Natl. Acad. Sci. USA 80, 4169.
Heumann R., Lindholm D., Brandtlow C., Meyer M., Radeke M. J., Misko Y., Shooter E., and Thoenen H. (1987)Proc. Natl. Acad. Sci. USA 84, 8735.
Bandtlow C. E., Heumann R., Schwab M. E., and Thoenen H. (1987)EMBO J. 6, 891.
Meuller H. W., Ignatius M. J., Hangen D. H., and Shooter E. M. (1986)J. Cell. Biol. 102, 393.
Aloe L., Cozzari C., Calissano P., and Levi-Montalcini R. (1981)Nature 291, 413.
Goedert M., Stöckli K., and Otten U. (1981)Proc. Natl. Acad. Sci. USA 78, 5895.
Ruit K. G., Elliott J. L., Osborne P. A., Yan Q., and Snider W. D. (1992)Neuron 8, 573.
Barde Y.-A., Ed D., and Thoenen H. (1982)EMBO J. 1, 549.
Leibrock J., Lottspeich F., Hohn A., Hofer M., Hengerer B., Masialowski P., Thoenen H., and Barde Y.-A. (1989)Nature 341, 149.
Hohn A., Leibrock J., Bailey K., and Barde Y.-A. (1990)Nature 344, 339.
Maisonpierre P. C., Belluscio L., Friedman B., Alderson R. F., Wiegand S. J., Furth M. E., Lindsay R. M., and Yancopoulos G. D. (1990)Neuron 5, 501.
Ernfors P., Wetmore C., Olsom L., and Persson H. (1990)Proc. Natl. Acad. Sci. USA 87, 5454.
Rosenthal A., Goeddel D. V., Nguyen T., Lewis M., Shih A., Laramee G. R., Nikolics K., and Winslow J. W. (1990)Neuron 4, 767.
Rende M., Muir D., Ruoslahti E., Hagg T., Varon S., and Manthorpe M. (1992)Glia 5, 25.
Hallböök F., Ibanez C. F., and Persson H. (1991)Neuron 6, 845.
Berkemeier L. R., Winslow J. W., Kaplan D. R., Nikolics K., Goeddel D. V., and Rosenthal A. (1991)Neuron 7, 857.
Landa K. B., Adler R., Manthorpe M., and Varon S. (1980)Dev. Biol. 74, 401.
Manthorpe M., Ray J., Pettmann B., and Varon S. (1989) inCholinergic Neurotrophic Factors vol. 3 (Rush R., ed.) Wiley, New York, pp. 135–146.
Hofer M., Pagliusi S. R., Hohn A., Leibrock J., and Barde Y.-A. (1990)EMBO J. 9, 2459.
Phillips H. S., Hains J. M., Laramee G. R., Rosenthal A., and Winslow J. W. (1990)Science 250, 290.
Wetmore C., Cao Y., Patterson R. F., and Olson L. (1991)Proc. Natl. Acad. Sci. USA 88, 9843.
Lindsay R. M., Thoenen H., and Barde Y.-A. (1985)Dev. Biol. 112, 319.
Davies A. M., Thoenen H., and Barde Y.-A. (1986)J. Neurosci. 6, 1897.
Acheson A., Barde Y.-A., and Thoenen H. (1987)Exp. Cell Res. 170, 56.
Hofer M. M. and Barde Y.-A. (1988)Nature (Lond.) 331, 261.
Johnson J. E., Barde Y.-A., Schwab M. E., and Thoenen H. (1986)J. Neurosci. 6, 3031.
Rodriguez-Tebar A., Jeffrey P., Thoenen H., and Barde Y.-A. (1989)Dev. Biol. 136, 296.
Thanos S., Baehr M., Barde Y.-A., and Vanselow J. (1989)Eur. J. Neurosci. 1, 19.
Barde Y.-A. (1989)Neuron 2, 1525.
Alderson R. F., Alterman A. L., Barde Y.-A., and Lindsay R. M. (1990)Neuron 5, 297.
Hyman C., Hofer M., Barde Y.-A., Juhasz M., Yancopolous G. D., Squinto S. P., and Lindsay R. M. (1991)Nature 350, 230.
Meyer M., Matsuoka L., Wetmore C., Olson L., and Thoenen H. (1992)J. Cell Biol. 119, 45.
Acheson A., Barker P. A., Alderson F., Miller F. D., and Murphy R. A. (1991)Neuron 7, 265.
Ernfors P., Wetmore C., Olson L., and Persson H. (1990)Neuron 5, 511.
Maisonpierre P. C., Belluscio L., Squinto S., Ip N. Y., Furth M. E., Lindsay R. M., and Yancopoulos G. D. (1990)Science 247, 1446.
Stöckli K. A., Lottspeich F., Sendtner M., Masiakowski P., Carroll P., Goetz R., Lindholm D., and Thoenen H. (1989)Nature 342, 920.
Friedman B., Ip N. Y., Helgren M. E., Rudge J., Rakowski T., Fu L., Morissey D., Wiegand S. J., and Lindsay R. M. (1991)J. Neurosci. Abstr. 17, 446.17.
Barbin G., Manthorpe M., and Varon S. (1984)J. Neurochem. 43, 1468.
Arakawa Y., Sendtner M., and Thoenen H. (1990)J. Neurosci. 10, 3507.
Wong V., Arriaga R., and Lindsay R. M. (1990)J. Neurosci. Abstr. 16, 484.0.
Oppenheim R. W., Prevette D., Qin-Wei Y., Collins F., and MacDonald J. (1991)Science 251, 1616.
Sendtner M., Kreutzberg G. W., and Thoenen H. (1990)Nature 345, 440.
Williams L. R., Manthorpe M., Neito-Sampedro M., Cotman C. W., and Varon S. (1984)Int. J. Dev. Neurosci. 2, 177.
Sendtner M., Stöckli K. A., and Thoenen H. (1992)J. Cell Biol. 118, 139.
Seniuk N., Harce M. A., Dunn R. J., and Richardson P. M. (1991)J. Neurosci. Abstr. 17, 446.4.
Rabinovsky E. D., Smith G. M., Browder D. P., Shine H. D., and McManaman J. L. (1992)J. Neurosci. Res. 31, 188.
Lindsay R. M. (1988)J. Neurosci. 8(7), 2394.
Kuffler D. P. and Megwinoff O. (1994)J. Neurobiol., in press.
Oppenheim R. W. (1991)Annu. Rev. Neurosci. 14, 453.
Bennett M. R., Lai K., and Nurcombe V. (1980)Brain Res. 190, 537.
Dribin L. B. and Barrett J. N. (1990)Dev. Biol. 118, 209.
Henderson C. E., Huchet M., and Changeux J. P. (1981)Proc. Natl. Acad. Sci. USA 78, 2625.
Henderson C. E., Huchet M., and Changeux J. P. (1983)Nature 302, 609.
Calof A. L. and Reichardt L. F. (1985)Dev. Biol. 106, 194.
Nurcombe V., Hill M. A., Eagleson K. L., and Bennett M. R. (1984)Brain Res. 291, 19.
O'Brien R. J. and Fischbach G. D. (1986)J. Neurosci. 6(11), 3265.
Arakawa Y., Sendtner M., and Thoenen H. (1990)J. Neurosci. 10, 3507.
Bloch-Gallego E., Huchet M., El M'Hamdi H., Xie F.-K., Tanaka H., and Henderson C. E. (1991)Development 111, 221.
McManaman J., Crawford F., Clark R., Richker J., and Fuller F. (1989)J. Neurochem. 53, 1763.
Kuffler D. P. (1990)J. Comp. Neurol. 302, 729.
Salonen V., Peltonen J., Roytta R., and Virtanen I. (1987)J. Neurocytol. 16, 713.
Kuffler D. P. and Luethi T. (1993)J. Neurobiol. 24, 515.
Baier H. and Bonhoeffer F. (1992)Science 255, 472.
Snow D. M. and Letourneau P. C. (1992) (CS-PG).J. Neurobiol. 23, 322.
Bonhoeffer F. and Huf J. (1982)EMBO J. 1, 427.
Stahl B., Mueller B., von Boxberg Y., Cox E. C., and Bonhoeffer F. (1990)Neuron 5, 734.
Stahl B., Boxberg Y., Muller B., Walter J., Schwartz U., and Boenhoeffer F. (1991)Cold Spring Harb. Symp. Quant. Biol. 55, 351.
Kater S. B., Mattson M. P., Cohan C., and Connor J. (1988)Trends Neurosci. 11, 315.
Gundersen R. W. and Barrett J. N. (1979)Science 206, 1079.
Gundersen R. W. and Barrett J. N. (1980)J. Cell Biol. 87, 546.
Davies A. M., Bandtlow C., Heuman D. R., Korsching S., Rohrer R., and Thoenen H. (1987)Nature 326, 353.
Lundborg G. F., Longo M., and Varon S. (1982)Brain Res. 232, 157.
Kuffler D. P. (1986)J. Comp. Neurol. 249, 57.
Kuffler D. P. (1987)J. Exp. Biol. 132, 151.
Kuffler D. P. (1989)J. Comp. Neurol. 281, 416.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kuffler, D.P. Promoting and directing axon outgrowth. Mol Neurobiol 9, 233–243 (1994). https://doi.org/10.1007/BF02816122
Issue Date:
DOI: https://doi.org/10.1007/BF02816122