Abstract
Axonal outgrowth is generally thought to be controlled by direct interaction of the lead growth cone with guidance cues, and, in trailing axons, by fasciculation with pioneer fibers. Responses of axons and growth cones were examined as cultured retinal ganglion cell (RGC) axons encountered repellent cues. Either contact with cells expressing ephrins or mechanical probing increased the probability of lead growth cone retraction. Lateral extension of filopodia and lamellipodia hundreds of microns behind the lead growth cone was correlated with its collapse. Transmission electron microscopy showed that some of the lateral extensions originate from the pioneer axon, whereas others represent growth cones of defasciculating trailing axons.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Sperry, R. W. Chemoaffinity in the orderly growth of nerve fiber patterns and connections. Proc. Natl. Acad. Sci. USA 50, 703–710 (1963).
Drescher, U., Bonhoeffer, F. & Muller, B. K. The Eph family in retinal axon guidance. Curr. Opin. Neurobiol. 7, 75–80 (1997).
Nakamoto, M. et al. Topographically specific effects of ELF-1 on retinal axon guidance in vitro and retinal axon mapping in vivo. Cell 86, 755–766 (1996).
Roskies, A., Friedman, G. C. & O'Leary, D. D. Mechanisms and molecules controlling the development of retinal maps. Perspect. Dev. Neurobiol. 3, 63–75 (1995).
Sanes, J. R. Topographic maps and molecular gradients. Curr. Opin. Neurobiol. 3, 67–74 (1993).
Drescher, U. et al. In vitro guidance of retinal ganglion cell axons by RAGS, a 25 kDa tectal protein related to ligands for Eph receptor tyrosine kinases. Cell 82, 359–370 (1995).
Monschau, B. et al. Shared and distinct functions of RAGS and ELF-1 in guiding retinal axons. EMBO J. 16, 1258–1267 (1997).
Cheng, H. J., Nakamoto, M., Bergemann, A. D. & Flanagan, J. G. Complementary gradients in expression and binding of ELF-1 and Mek4 in development of the topographic retinotectal projection map. Cell 82, 371–381 (1995).
Bonhoeffer, F. & Gierer, A. How do retinal axons find their targets on the tectum? Trends Neurosci. 7, 378–381 (1984).
Nakamura, H. & O'Leary, D. D. Inaccuracies in initial growth and arborization of chick retinotectal axons followed by course corrections and axon remodeling to develop topographic order. J. Neurosci. 9, 3776–3795 (1989).
Simon, D. K. & O'Leary, D. D. Limited topographic specificity in the targeting and branching of mammalian retinal axons. Dev. Biol. 137, 125–134 (1990).
Simon, D. K., Roskies, A. L. & O'Leary, D. D. Plasticity in the development of topographic order in the mammalian retinocollicular projection. Dev. Biol. 162, 384–393 (1994).
Gallo, G. & Letourneau, P. C. Localized sources of neurotrophins initiate axon collateral sprouting. J. Neurosci. 18, 5403–5414 (1998).
Williams, C. V., Davenport, R. W., Dou, P. & Kater, S. B. Developmental regulation of plasticity along neurite shafts. J. Neurobiol. 27, 127–140 (1995).
McCaig, C. D. Nerve branching is induced and oriented by a small applied electric field. J. Cell Sci. 95, 605–615 (1990).
Bastmeyer, M. & O'Leary, D. D. Dynamics of target recognition by interstitial axon branching along developing cortical axons. J. Neurosci. 16, 1450–1459 (1996).
O'Leary, D. D. & Terashima, T. Cortical axons branch to multiple subcortical targets by interstitial axon budding: implications for target recognition and "waiting periods". Neuron 1, 901–910 (1988).
O'Leary, D. D. & Stanfield, B. B. Occipital cortical neurons with transient pyramidal tract axons extend and maintain collaterals to subcortical but not intracortical targets. Brain Res. 336, 326–333 (1985).
Szebenyi, G., Callaway, J. L., Dent, E. W. & Kalil, K. Interstitial branches develop from active regions of the axon demarcated by the primary growth cone during pausing behaviors. J. Neurosci. 18, 7930–7940 (1998).
Davenport, R. W., Thies, E., Zhou, R. & Nelson, P. G. Cellular localization of ephrin-A2, -A5 and other functional guidance cues underlie retinotopic development across species. J. Neurosci. 18, 975–986 (1998).
Davenport, R. W., Thies, E. & Nelson, P. G. Cellular localization of guidance cues in the establishment of retinotectal topography. J. Neurosci. 16, 2074–2085 (1996).
Davenport, R. W., Dou, P., Rehder, V. & Kater, S. B. A sensory role for neuronal growth cone filopodia. Nature 361, 721–724 (1993).
Burmeister, D. W., Rivas, R. J. & Goldberg, D. J. Substrate-bound factors stimulate engorgement of growth cone lamellipodia during neurite elongation. Cell. Motil. Cytoskeleton 19, 255–268 (1991).
Goldberg, D. J., Burmeister, D. W. & Rivas, R. J. in The Nerve Growth Cone (eds. Letourneau, P. C., Kater, S. B. & Macagno, E. R.) 79–96 (Raven, New York, 1991).
Vanegas, H. Comparative Neurology of the Optic Tectum (Plenum, New York, 1984).
Harris, W. A. & Holt, C. E. From tags to RAGS: chemoaffinity finally has receptors and ligands. Neuron 15, 241–244 (1995).
Frisen, J. et al. Ephrin-A5 (AL-1/RAGS) is essential for proper retinal axon guidance and topographic mapping in the mammalian visual system. Neuron 20, 235–243 (1998).
Tanaka, E., Ho, R. & Kirschner, M. W. The role of microtubule dynamics in growth cone motility and axonal growth. J. Cell Biol. 128, 139–155 (1995).
Gierer, A. Directional cues for growing axons forming the retinotectal projection. Development 101, 479–489 (1987).
Udin, S. B. & Fawcett, J. W. Formation of topographic maps. Annu. Rev. Neurosci. 11, 289–327 (1988).
Stahl, B. et al. Directional cues for retinal axons. Cold Spring Harb. Symp. Quant. Biol. 55, 351–357 (1990).
Simon, D. K. & O'Leary, D. D. Responses of retinal axons in vivo and in vitro to position-encoding molecules in the embryonic superior colliculus. Neuron 9, 977–989 (1992).
Baier, H. & Bonhoeffer, F. Axon guidance by gradients of a target-derived component. Science 255, 472–475 (1992).
Goldberg, S. Studies on the mechanics of development of the visual pathways in the chick embryo. Dev. Biol. 36, 24–43 (1974).
Thanos, S. & Bonhoeffer, F. Investigations on the development and topographic order of retinotectal axons: anterograde and retrograde staining of axons and perikarya with rhodamine in vivo. J. Comp. Neurol. 219, 420–430 (1983).
Thanos, S., Bonhoeffer, F. & Rutishauser, U. Fiber–fiber interaction and tectal cues influence the development of the chicken retinotectal projection. Proc. Natl. Acad. Sci. USA 81, 1906–1910 (1984).
Burrill, J. D. & Easter, S. S. Jr. The first retinal axons and their microenvironment in zebrafish: Cryptic pioneers and the pretract. J. Neurosci. 15, 2935–2947 (1995).
Harris, W. A., Holt, C. E. & Bonhoeffer, F. Retinal axons with and without their somata, growing to and arborizing in the tectum of Xenopus embryos: a time-lapse video study of single fibres in vivo. Development 101, 123–133 (1987).
Thanos, S. & Bonhoeffer, F. Axonal arborization in the developing chick retinotectal system. J. Comp. Neurol. 261, 155–164 (1987).
Bodick, N. & Levinthal, C. Growing optic nerve fibers follow neighbors during embryogenesis. Proc. Natl. Acad. Sci. USA 77, 4374–4378 (1980).
Roskies, A. L. & O'Leary, D. D. Control of topographic retinal axon branching by inhibitory membrane-bound molecules. Science 265, 799–803 (1994).
Neale, E., MacDonald, R. L. & Nelson, P. G. Intracellular horseradish peroxidase injections for correlation of light and electron microscopic anatomy with synaptic physiology with cultured mouse spinal cord neurons. Brain Res. 152, 265–282 (1978).
Acknowledgements
For sharing their technical expertise, the authors thank E. Neale, L. Williamson, M. Bastmeyer and G. Gallo. We also thank P. Nelson for providing support and inspiration, along with V. Rehder and P. Atkinson for reading and providing criticisms of the manuscript.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Davenport, R., Thies, E. & Cohen, M. Neuronal growth cone collapse triggers lateral extensions along trailing axons. Nat Neurosci 2, 254–259 (1999). https://doi.org/10.1038/6360
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/6360
This article is cited by
-
Profilin and Mical combine to impair F-actin assembly and promote disassembly and remodeling
Nature Communications (2021)
-
Changes in expression of Class 3 Semaphorins and their receptors during development of the rat retina and superior colliculus
BMC Developmental Biology (2014)
-
Transient axonal glycoprotein-1 (TAG-1) and laminin-α1 regulate dynamic growth cone behaviors and initial axon direction in vivo
Neural Development (2008)