Summary
Nodal sprouting in response to axonal degeneration was studied in silver-stained, wholemount preparations of the thin, sheet-like mouse muscles tensor faciae latae (TFL) and the inferior and superior gluteus maximus. Axon degeneration in TFL and gluteus was produced by cutting the L4 spinal nerve (partial denervation). Axon degeneration in the gluteus was also produced by superior gluteal and TFL nerve section (hemidenervation).
Two days after partial or hemidenervation motor nerve nodal sprouts begin to appear in the intramuscular nerves. Sprout growth is rapid, since only a small percentage of sprouts are ever seen not to terminate at endplates. Sprouts continue to appear for at least three weeks after partial denervation, when there are up to five times as many endplates innervated by sprouts as by remaining intact axons. Sprouts arise at nodes near the denervated endplates, which they innervate by growing directly down the degenerating nerve. Sprout initiation proceeds sequentially in partly and hemidenervated muscles, since the average length of sprouts contacting endplates increases with time. Analysis of silver-stained muscles by combined light and electron microscopy shows that this sequential development is unlikely to be a consequence of slow growth and maturation of submicroscopic sprouts initiated nonsequentially throughout the intramuscular nerves.
The observations are consistent with a nodal sprouting mechanism which requires a cellular or structural change in the denervated Schwann cell pathway to spread disto-proximally from the terminal ends of the nerves and thereby to permit the growth of nodal sprouts. The initiation of sprout growth may require a diffusible substance from degenerating nerve or denervated muscle.
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References
Betz, W. J., Caldwell, J. H. &Ribchester, R. R. (1980) Sprouting of active nerve terminals in partially inactive muscles of the rat.Journal of Physiology 303, 281–97.
Bonhoeffer, F. &Huf, J. (1980) Recognition of cell types by axonal growth conesin vitro.Nature 288, 162–4.
Bray, D. (1973) Model for membrane movements in the axonal growth cone.Nature 244, 93–5.
Brown, M. C. &Holland, R. L. (1979) A central role for denervated tissues in causing sprouting.Nature 282, 724–6.
Brown, M. C., Holland, R. L. &Hopkins, W. G. (1981a) Motor nerve sprouting.Annual Review of Neuroscience 4, 17–42.
Brown, M. C., Holland, R. L., Hopkins, W. G. &Keynes, R. J. (1981b) An assessment of the spread of the signal for terminal sprouting within and between muscles.Brain Research 210, 145–51.
Brown, M. C., Holland, R. L. &Ironton, R. (1978) Is the stimulus for motoneurone terminal sprouting localised?Journal of Physiology 282, 7–8P.
Brown, M. C., Holland, R. L. &Ironton, R. (1980) Nodal and terminal sprouting from motor nerves in fast and slow muscles of the mouse.Journal of Physiology 306, 493–510.
Brown, M. C. &Ironton, R. (1977) Motor neurone sprouting induced by prolonged tetrodotoxin block of nerve action potentials.Nature 265, 459–61.
Brown, M. C. &Ironton, R. (1978) Sprouting and regression of neuromuscular synapses in partially denervated mammalian muscles.Journal of Physiology 278, 325–48.
Cajal, S. Ramón y (1909)Histologie du Système Nerveux de l'Homme et des Vertèbres. Vol. 1, pp. 597–600. Madrid: Instituto Ramón y Cajal.
Cajal, S. Ramón y (1928)Degeneration and Regeneration of the Nervous System (translated byMay, R. M.), pp. 172–182. London: Oxford University Press.
Causey, G. &Hoffman, H. (1955) Axon sprouting in partially denervated nerves.Brain 78, 661–8.
Duchen, L. W. &Strich, S. J. (1968) The effects of botulinum toxin on the pattern of innervation of skeletal muscle of the mouse.Quarterly Journal of Experimental Physiology 53, 84–9.
Edds, M. V. (1949) Experiments on partially deneurotized nerves.Journal of Experimental Zoology 111, 211–26.
Edds, M. V. (1953) Collateral nerve regeneration.Quarterly Review of Biology 28, 260–76.
Friede, R. L. &Martinez, A. J. (1970) Analysis of axon sheath relations during early Wallerian degeneration.Brain Research 19, 199–212.
Gray, E. G. &Guillery, R. W. (1961) The basis of silver staining of synapses of the mammalian spinal cord: a light and electron microscope study.Journal of Physiology 157, 581–88.
Gundersen, R. W. &Barrett, J. N. (1979) Neuronal chemotaxis: chick dorsal-root axons turn towards high concentrations of nerve growth factor.Science 206, 1079–80.
Gutmann, E. &Young, J. Z. (1944) The reinnervation of muscle after varying periods of atrophy.Journal of Anatomy 78, 15–43.
Hoffman, H. (1950) Local reinnervation of partially denervated muscle: a histophysiological study.Australian Journal of Experimental Biology and Medical Science 28, 383–97.
Hoffman, H. (1952) Acceleration and retardation of the process of axon sprouting in partially denervated muscles.Australian Journal of Experimental Biology and Medical Science 30, 541–66.
Holland, R. L. &Brown, M. C. (1980) Postsynaptic transmission block can cause sprouting of a motor nerve.Science 207, 649–51.
Holland, R. L. &Brown, M. C. (1981) Nerve growth in botulinum toxin-poisoned muscles.Neuroscience (in press).
Holmes, W. &Young, J. Z. (1942) Nerve regeneration after immediate and delayed suture.Journal of Anatomy 77, 63–96.
Ironton, R., Brown, M. C. &Holland, R. L. (1978) Stimuli to intramuscular nerve growth.Brain Research 156, 351–4.
Letourneau, P. C. (1975) Cell-to-substratum adhesion and guidance of axonal elongation.Developmental Biology 44, 92–101.
Letourneau, P. C. (1978) Chemotactic response of nerve fiber elongation to nerve growth factor.Developmental Biology 66, 183–96.
Lopresti, V., Macagno, E. R. &Levinthal, C. (1973) Structure and development of neuronal connections in isogenic organisms: cellular interactions in the development of the optic lamina of Daphnia.Proceedings of the National Academy of Sciences (U.S.A.) 70, 433–7.
Lubinska, L. (1977) Early course of Wallerian degeneration in myelinated fibers of the rat phrenic nerve.Brain Research 130, 47–63.
Menesini, M. G., Chen, J. S. &Levi-Montalclni, R. (1978) Sympathetic nerve fibres ingrowth in the central nervous system of neonatal rodent upon intracerebral NGF injections.Archives Italiennes de Biologie 116, 53–84.
Namba, T., Nakamura, T. &Grob, D. (1967) Staining for nerve fibre and cholinesterase activity in fresh frozen sections.American Journal of Clinical Pathology 47, 74–7.
O'brien, R. A. D., Östberg, A. J. C. &Vrbová, G. (1978) Observations on the elimination of polyneuronal innervation in developing mammalian skeletal muscle.Journal of Physiology 282, 571–82.
Pestronk, A. &Drachman, D. B. (1978) Motor nerve sprouting and acetylcholine receptors.Science 199, 1223–5.
Riley, D. A. (1977) Spontaneous elimination of nerve terminals from the endplates of developing skeletal myofibers.Brain Research 134, 279–85.
Slack, J. R., Hopkins, W. G. &Williams, M. N. (1979) Nerve sheaths and motoneurone collateral sprouting.Nature 282, 506–7.
Sunderland, S. (1978)Nerves and Nerve Injuries. 2nd edn. London: Churchill Livingstone.
Tennyson, V. M. (1970) The fine structure of the axon and growth cone of the dorsal root neuroblast of the rabbit embryo.Journal of Cell Biology 44, 62–79.
Thomas, P. K. (1964) Changes in the endoneurial sheaths of peripheral myelinated nerve fibres during Wallerian degeneration.Journal of Anatomy 98, 175–82.
Thompson, W. &Jansen, J. K. S. (1977) The extent of sprouting of remaining motor units in partly denervated immature and adult rat soleus muscle.Neuroscience 2, 523–36.
Yamada, K. M., Spooner, B. S. &Wessells, N. K. (1970) Axon growth: roles of neurofilaments and microtubules.Proceedings of the National Academy of Sciences (U.S.A.) 66, 1206–12.
Yamada, K. M., Spooner, B. S. &Wessells, N. K. (1971) Ultrastructure and function of growth cones and axons of cultured nerve cells.Journal of Cell Biology 49, 614–35.
Zacks, S. I. &Saito, A. (1969) Uptake of exogeneous horseradish peroxidase by coated vesicles in mouse neuromuscular junction.Journal of Histochemistry and Cytochemistry 17, 161–70.
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Hopkins, W.G., Slack, J.R. The sequential development of nodal sprouts in mouse muscles in response to nerve degeneration. J Neurocytol 10, 537–556 (1981). https://doi.org/10.1007/BF01262589
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DOI: https://doi.org/10.1007/BF01262589