Evidence for a motor nerve growth factor

Slack, J.R.; Hopkins, William G.; Pockett, Susan

doi:10.1002/mus.880060402

Cited by 67 publications

(19 citation statements)

References 106 publications

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“…The sprouting we observed nearby regenerating muscle fibers is probably related to the phenomenon of terminal sprouting that occurs after partial denervation (Brown et al, 1980;Slack and Pockett, 198 1;Pockett and Slack, 1982;Slack et al, 1983) or inactivation of muscles (Betz et al, 1980;Holland and Brown, 1980). In some of the cases, the sprouting also seemed to be confined to junctions in close proximity to the affected muscle fibers (Slack and Pockett, 198 1;Pockett and Slack, 1982).…”

Section: Discussionmentioning

confidence: 72%

Regenerating muscle fibers induce directional sprouting from nearby nerve terminals: studies in living mice

Mier

Lichtman

1994

J. Neurosci.

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The principal aim of this work was to better understand how regenerating muscle fibers become innervated in adult animals. To induce muscle regeneration, individual identified muscle fibers in a mouse were damaged with a laser focused through a microscope. The muscle fiber that degenerated and the muscle fiber that was formed in its place were followed by viewing the same site repeatedly over a period of 2 d to 40 weeks. Commonly, the nerve terminal innervating the irradiated muscle fiber partially retracted during muscle fiber degeneration, and then sprouted to innervate the regenerating muscle fiber at the same site it had previously innervated the muscle fiber that was damaged. During the early phase of muscle regeneration we also observed sprouts originating from nerve terminals on adjacent muscle fibers. The new nerve growth was a response to the regenerating muscle fiber rather than to the degenerated fiber it replaced because repeated damage of the same site every 2–3 d over a 10 d period (to prevent regeneration) did not cause any sprouting. The direction of the sprouts on adjacent muscle fibers showed a bias toward the regenerating muscle fiber, although they avoided the region occupied by the original nerve terminal. Forty percent of the sprouts managed to reach the regenerated fiber. Nonetheless, by 11 d after muscle fiber damage, all sprouts had regressed, leaving the new fiber innervated by the same motor axon that innervated the fiber that was damaged. On the other hand, when the overlying nerve terminal as well as the muscle fiber was damaged, the sprouts from nearby muscle fibers were both more numerous and more stable, and in five cases we observed two or more new synaptic junctions on the regenerating fiber originating from different axons. In one case we witnessed a protracted competition between the original motor axon as it sprouted back and the sprouts from nearby junctions for sole innervation of the regenerate. Ultimately, the surviving sprouts myelinated and became the permanent and exclusive input to the new fiber. These results indicate that regenerating muscle fibers emit a signal that induces directional sprouting from nearby undamaged nerve terminals. Reinnervation of the regenerating muscle fiber by one axon apparently prevents the maintenance of such neurites. Because the process of muscle regeneration shares many features in common with myogenesis during embryonic development, it is likely that developing muscle fibers present an analogous stimulus to ingrowing motor axons.(ABSTRACT TRUNCATED AT 400 WORDS)

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Section: Discussionmentioning

confidence: 72%

Regenerating muscle fibers induce directional sprouting from nearby nerve terminals: studies in living mice

Mier

Lichtman

1994

J. Neurosci.

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“…PNI is localized to the neuromuscular junction (32) and prevents degradation of myotube extracellular matrix by myoblast uPA/ plasmin (41). PNI released by muscle fibers at synaptic regions would be consistent with target-derived factor(s) diffusing and then anchoring to basal lamina sites (14,42,43). Such mechanisms for establishing polyneuronal innervation and its elimination persist into adulthood (44), although at a slower rate, and might be uncovered or reactivated by experimental denervation and reinnervation (11).…”

Section: Resultsmentioning

confidence: 99%

Rapid neural regulation of muscle urokinase-like plasminogen activator as defined by nerve crush.

Hantaı̈

Rao

Festoff

1990

Proc. Natl. Acad. Sci. U.S.A.

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Muscle plasminogen activators (PAs), such as urokinase-like PA and, to a lesser extent, tissue PA, increase dramatically after denervation induced by axotomy. The PA/plasmin system has also been implicated in degradation of specific components of the muscle fiber basement membrane after local activation of plasminogen. These results suggest that neural regulation of muscle extracellular matrix metabolism accompanies or precedes regeneration after injury and is mediated by activation of PAs. In the present study, we have used nerve crush to explore the neural regulation of muscle PA activities directly after subtotal axon interruption and during the process of reinnervation. Muscle contraction after nerve stimulation and estimation of choline acetyltransferase activity were used to monitor reinnervation. Within 24 hr of nerve crush, muscle urokinase (but not tissue PA) activity rose in soluble and membrane-bound muscle fractions, as shown by an amidolytic assay and a fibrin zymography. Membrane-bound activity was 5-fold higher than cytosol activity, but there was no shift between cellular compartments during the time course of denervation. Coincident with the return of choline acetyltransferase activity and muscle contractility, muscle urokinase returned almost to baseline levels. These results show tight regulation of muscle urokinase levels by some neural influence.When muscle is deprived ofits innervation, experimentally or by disease, the nerve terminals degenerate, are phagocytized, and are completely engulfed by Schwann cells in less than 3 days (1, 2). The earliest events in this pathophysiologic process are at the level of the membrane. Subsequently, the muscle fibers are left denervated and they respond to this condition with a variety of metabolic alterations, the most dramatic, but late, event being atrophy (3). The earliest changes after denervation are located at the muscle cell surface and include the loss of endplate-specific 16S acetylcholinesterase (4) and reduction offibronectin (5). The mechanism of these surface alterations appears to be activation of neutral proteases, serine proteases and metalloproteases, respectively. After a few days lag, intact axons make new connections with the denervated endplates by a process of collateral or ultraterminal outgrowth arising from the neuromuscular junction or the subterminal nodes of the surviving axons and functional neuromuscular connections begin to reform (1, 6-9).Our interest has been in the mechanism(s) controlling the initiation of these events and, in particular, the regulation of muscle serine protease activity. We have shown that total sciatic neurectomy was followed by a marked time-dependent increase in urokinase-like plasminogen activator (uPA)

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“…The phenomenon "natural cell death" and the role of the target have been shown very clearly for chick spinal motor neurons that depend on their peripheral target, skeletal muscle, during a critical period (see Hamburger, 1977;Slack et aL, 1983). Motor neuron cell death in the chick starts at Embryonie Days 5.5-6, (E5.5-6), a time at which the motor neurons have differentiated and assembled in the lateral motor columns, their axons projecting correctly to the peripheral target sites (Land-1 To whom correspondence should be addressed.…”

Section: Introductionmentioning

confidence: 99%

Muscle-derived factors that support survival and promote fiber outgrowth from embryonic chick spinal motor neurons in culture

Dohrmann

Edgar

Sendtner

et al. 1986

Developmental Biology

156

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The purpose of the experiments reported is to provide an unambiguous demonstration that embryonie skeletal muscle contains factors that act directly on embryonie spinal motor neurons both to support their survival and to stimulate the outgrowth of neurites. Cells of lumbar and brachial ventral spinal cords from 6-day-old chick embryos were separated by centrifugation in a two-step metrizamide gradient, and a motor neuron enriched fraction was obtained. Motor neurons were identified by retrogradely labeling with rhodamine isothiocyanate, and were enriched fourfold in the motor neuron fraction relative to unfractionated cells. In culture, the isolated motor neurons died within 3-4 days unless they were supplemented with embryonie chick skeletal muscle extract. Two functionally distinct entities separable by ammonium sulfate precipitation were responsible for the effects of muscle extracts on motor neurons. The 0-25% ammonium sulfate precipitate contained molecules that alone bad no effect on neuronal survival but when bound to polyornithine-coated culture substrata, stimulated neurite outgrowth and potentiated the survival activity present in muscle. Mostofthis activity was due to a laminin-like molecule being immunoprecipitated with antisera against laminin, and immunoblotting demonstrated the presence of both the A and B chains of laminin. A long-term survival activity resided in the 25-70% ammonium sulfate fraction, and its apparent total and specific activities were strongly dependent on the culture substrate. In contrast to the motor neurons, the cells from the other metrizamide fraction (including neuronal cells) could be kept in culture for a prolonged time without addition of exogenous factor(s).

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Evidence for a motor nerve growth factor

Cited by 67 publications

References 106 publications

Regenerating muscle fibers induce directional sprouting from nearby nerve terminals: studies in living mice

Regenerating muscle fibers induce directional sprouting from nearby nerve terminals: studies in living mice

Rapid neural regulation of muscle urokinase-like plasminogen activator as defined by nerve crush.

Muscle-derived factors that support survival and promote fiber outgrowth from embryonic chick spinal motor neurons in culture

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