N-cadherin expression in developing, adult and denervated chicken neuromuscular system: accumulations at both the neuromuscular junction and the node of Ranvier

Development ◽  
1994 ◽  
Vol 120 (1) ◽  
pp. 1-11 ◽  
Author(s):  
C. Cifuentes-Diaz ◽  
M. Nicolet ◽  
D. Goudou ◽  
F. Rieger ◽  
R.M. Mege
Keyword(s):  
Neuromuscular Junction ◽  
Schwann Cells ◽  
Basal Lamina ◽  
Cellular Localization ◽  
Node Of Ranvier ◽  
Muscle Fibres ◽  
Neuromuscular System ◽  
Distal Stump ◽  
Denervated Muscle

N-cadherin, a member of the Ca(2+)-dependent cell adhesion molecule family plays essential roles in morphogenesis and histogenesis. N-cadherin has been shown in vitro to promote myoblast fusion and neurite outgrowth. We report here the cellular localization of N-cadherin during development and regeneration of the chick neuromuscular system. N-cadherin was uniformly expressed along the surface of myoblasts and myotubes of E6 limb muscles. Later, as synaptogenesis and secondary myogenesis proceeded, N-cadherin expression was down-regulated and restricted to some large-diameter fibres, then to the areas of contact between few myofibres and subsequently disappeared by embryonic day 17, suggesting that this cadherin may be implicated predominantly in fusion of primary myoblasts and, at lower degree, of secondary myoblasts. The presence of N-cadherin in muscle during the period of nerve trunk ingrowth and its down-regulation after synaptogenesis suggests that this molecule might be implicated in both processes. N-cadherin became accumulated at the neuromuscular junction only a few days after the first synaptic contacts were established and remained at the adult neuromuscular junction, suggesting a role of this molecule in the stabilization of the mature neuromuscular junction. In sciatic nerve, the level of N-cadherin expression remained unchanged from hatching to adult life. N-cadherin was widely distributed on the surface of myelinated fibres and on myelinating Schwann cells: in addition, it was concentrated at the node of Ranvier. At the ultrastructural level, the molecule was detected inside, at the surface and in the basal lamina of Schwann cells and also associated with endoneurial collagen. These observations suggest a role of N-cadherin in the structuring and stabilization of the myelin sheaths. After nerve injury, N-cadherin continued to be expressed by proliferating Schwann cells in the distal stump providing a substratum for regenerating axons. N-cadherin reappeared at the surface of denervated muscle fibres without disappearing from the former synaptic sites. It was detected not only in the sarcoplasm and on sarcolemma of denervated muscle fibres, but also in the basal lamina and in the extracellular matrix. The reexpression of N-cadherin at the surface of denervated muscle fibres suggests a role for this molecule in muscle reinnervation. The presence of N-cadherin in basal lamina and its association with collagen fibres raise questions about the release of N-cadherin in the extracellular space and the existence of a putative heterophilic ligand for N-cadherin.

scholarly journals Expression of cytotactin in the normal and regenerating neuromuscular system.

1989 ◽  
Vol 108 (2) ◽  
pp. 625-635 ◽  
Author(s):  
J K Daniloff ◽  
K L Crossin ◽  
M Pinçon-Raymond ◽  
M Murawsky ◽  
F Rieger ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Neuromuscular Junction ◽  
Schwann Cells ◽  
Node Of Ranvier ◽  
Myotendinous Junction ◽  
Neuromuscular System ◽  
Peripheral Nerve Damage ◽  
Neural Cell Adhesion ◽  
Developing Cerebellum

Cytotactin is an extracellular glycoprotein found in a highly specialized distribution during embryonic development. In the brain, it is synthesized by glia, not neurons. It is involved in neuron-glia adhesion in vitro and affects neuronal migration in the developing cerebellum. In an attempt to extend these observations to the peripheral nervous system, we have examined the distribution and localization of cytotactin in different parts of the normal and regenerating neuromuscular system. In the normal neuromuscular system, cytotactin accumulated at critical sites of cell-cell interactions, specifically at the neuromuscular junction and the myotendinous junction, as well at the node of Ranvier (Rieger, F., J. K. Daniloff, M. Pinçon-Raymond, K. L. Crossin, M. Grumet, and G. M. Edelman. 1986. J. Cell Biol. 103:379-391). At the neuromuscular junction, cytotactin was located in terminal nonmyelinating Schwann cells. Cytotactin was also detected near the insertion points of the muscle fibers to tendinous structures in both the proximal and distal endomysial regions of the myotendinous junctions. This was in striking contrast to staining for the neural cell adhesion molecule, N-CAM, which was accumulated near the extreme ends of the muscle fiber. Peripheral nerve damage resulted in modulation of expression of cytotactin in both nerve and muscle, particularly among the interacting tissues during regeneration and reinnervation. In denervated muscle, cytotactin accumulated in interstitial spaces and near the previous synaptic sites. Cytotactin levels were elevated and remained high along the endoneurial tubes and in the perineurium as long as muscle remained denervated. Reinnervation led to a return to normal levels of cytotactin both in inner surfaces of the nerve fascicles and in the perineurium. In dorsal root ganglia, the processes surrounding ganglionic neurons became intensely stained by anticytotactin antibodies after the nerve was cut, and returned to normal by 30 d after injury. These data suggest that local signals between neurons, glia, and supporting cells may regulate cytotactin expression in the neuromuscular system in a fashion coordinate with other cell adhesion molecules. Moreover, innervation may regulate the relative amount and distribution of cytotactin both in muscle and in Schwann cells.

scholarly journals Beta4 integrin is required for hemidesmosome formation, cell adhesion and cell survival.

1996 ◽  
Vol 134 (2) ◽  
pp. 559-572 ◽  
Author(s):  
J Dowling ◽  
Q C Yu ◽  
E Fuchs
Keyword(s):  
Cell Adhesion ◽  
Cell Survival ◽  
Schwann Cells ◽  
Basal Lamina ◽  
Epidermolysis Bullosa ◽  
Junctional Epidermolysis Bullosa ◽  
Human Disorder ◽  
Stratified Epithelia

The integrin heterodimer alpha 6 beta 4 is expressed in many epithelia and in Schwann cells. In stratified epithelia, alpha 6 beta 4 couple with BPAG1-e and BPAG2 to form hemidesmosomes, attaching externally to laminin and internally to the keratin cytoskeleton. To explore the function of this atypical integrin, and its relation to conventional actin-associated integrins, we targeted the removal of the beta 4 gene in mice. Tissues that express alpha 6 beta 4 are grossly affected. Stratified tissues are devoid of hemidesmosomes, display only a very fragile attachment to the basal lamina, and exhibit signs of degeneration and tissue disorganization. Simple epithelia which express alpha 6 beta 4 are also defective in adherence, even though they do not form hemidesmosomes. In the absence of beta 4, alpha 6 is dramatically downregulated, and other integrins do not appear to compensate for the loss of this heterodimer. These data have important implications for understanding integrin function in cell-substratum adhesion, cell survival and differentiation, and for understanding the role of alpha 6 beta 4 in junctional epidermolysis bullosa, an often lethal human disorder with pathology similar to our mice.

scholarly journals Age-Related Alterations at Neuromuscular Junction: Role of Oxidative Stress and Epigenetic Modifications

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1307
Author(s):  
Gabriella Dobrowolny ◽  
Alessandra Barbiera ◽  
Gigliola Sica ◽  
Bianca Maria Scicchitano
Keyword(s):  
Neuromuscular Junction ◽  
Neuromuscular Junctions ◽  
Epigenetic Modifications ◽  
Neuromuscular System ◽  
Molecular Alterations ◽  
Age Related ◽  
Fiber Number ◽  
Physical Abilities ◽  
Effects Of Aging

With advancing aging, a decline in physical abilities occurs, leading to reduced mobility and loss of independence. Although many factors contribute to the physio-pathological effects of aging, an important event seems to be related to the compromised integrity of the neuromuscular system, which connects the brain and skeletal muscles via motoneurons and the neuromuscular junctions (NMJs). NMJs undergo severe functional, morphological, and molecular alterations during aging and ultimately degenerate. The effect of this decline is an inexorable decrease in skeletal muscle mass and strength, a condition generally known as sarcopenia. Moreover, several studies have highlighted how the age-related alteration of reactive oxygen species (ROS) homeostasis can contribute to changes in the neuromuscular junction morphology and stability, leading to the reduction in fiber number and innervation. Increasing evidence supports the involvement of epigenetic modifications in age-dependent alterations of the NMJ. In particular, DNA methylation, histone modifications, and miRNA-dependent gene expression represent the major epigenetic mechanisms that play a crucial role in NMJ remodeling. It is established that environmental and lifestyle factors, such as physical exercise and nutrition that are susceptible to change during aging, can modulate epigenetic phenomena and attenuate the age-related NMJs changes. This review aims to highlight the recent epigenetic findings related to the NMJ dysregulation during aging and the role of physical activity and nutrition as possible interventions to attenuate or delay the age-related decline in the neuromuscular system.

scholarly journals Tissue culture observations relevant to the study of axon-Schwann cell interactions during peripheral nerve development and repair

1987 ◽  
Vol 132 (1) ◽  
pp. 21-34 ◽  
Author(s):  
R. P. Bunge
Keyword(s):  
Tissue Culture ◽  
Schwann Cell ◽  
Peripheral Nerve ◽  
Schwann Cells ◽  
Basal Lamina ◽  
Heparan Sulphate ◽  
Cell Contact ◽  
Myelinated Nerve ◽  
Nerve Development

During peripheral nerve development the Schwann cell population is expanded so that adequate numbers are available for ensheathment of both nonmyelinated and myelinated nerve fibres. As ensheathment of these fibres progresses each axon--Schwann cell unit becomes surrounded by a basal lamina, providing a unique microtubular framework within the peripheral nerve trunk. Tissue culture studies of pure populations of neurones and Schwann cells cultured separately and in combination indicate that a surface component on the axon provides a mitogenic signal to Schwann cells requiring cell-cell contact. Biochemical, electron microscopic and immunocytochemical analyses of these cultures indicate that Schwann cells in contact with axons are able to generate a basal lamina (containing type IV collagen, laminin and heparan sulphate proteoglycan) and fibrous collagen, without the aid of other cells, and that axonal contact is required for deposition of the basal lamina. The role of Schwann cells and the extracellular matrix they synthesize and organize, as well as the role of the other known products of the Schwann cells in the process of peripheral nerve regeneration, are discussed. It is suggested that the large numbers and advantageous position of the Schwann cells, as well as their ability to provide their own surfaces, a basal lamina and multiple secretory products, may account for their extraordinary ability to foster nerve fibre regeneration.

Acetylcholine receptors at the rat neuromuscular junction as revealed by deep etching

1982 ◽  
Vol 215 (1199) ◽  
pp. 147-154 ◽  
Keyword(s):  
Neuromuscular Junction ◽  
Basal Lamina ◽  
Acetylcholine Receptors ◽  
Postsynaptic Membrane ◽  
Muscle Fibres ◽  
Nerve Terminals ◽  
Single Muscle ◽  
Deep Etching ◽  
Collagenase Treatment ◽  
Regular Arrangement

Collagenase treatment of rat intercostal muscles yielded single muscle fibres in which the nerve terminals and basal lamina were removed allowing an unimpeded view of the ecternal surface of the postsynaptic membrane. This was revealed by deep etching of freeze-fractured preparations and appeared as a maze of folds separated by deep troughs, showing on the crests of the folds a densely packed population of protrusions about 8⋅5 nm in diameter. These densely packed protrusions ( ca . 9000 μm -2 ) are mainly confined to the postsynaptic regions of the sarcolemma and presumably represent the acetycholine receptor molecules, which are highly concenrated in these areas. The protrusions are generally tightly packed without obvious regular arrangement, but in some areas, usually on the tops of the crests, they are arranged into irregular rows normal to the long axis of the folds.

Electrophysiology and electron-microscopy of rat neuromuscular junctions after nerve degeneration

1968 ◽  
Vol 169 (1016) ◽  
pp. 289-306 ◽  
Keyword(s):  
Electron Microscopy ◽  
Schwann Cell ◽  
Neuromuscular Junction ◽  
Neuromuscular Junctions ◽  
Diaphragm Muscle ◽  
Nerve Degeneration ◽  
Muscle Membrane ◽  
Muscle Fibres ◽  
Denervated Muscle ◽  
End Plate

(1) Intracellular micro-electrodes and electron-microscopy were used to study normal and denervated end-plates in rat diaphragm muscle fibres. (2) In normal muscles 84.5 to 100% of the micro-electrode insertions were sufficiently close to the neuromuscular junction to detect miniature end-plate potentials. The structure of the normal neuromuscular junction had the usual 3-cell arrangement: muscle with synaptic folds, axon and Schwann cell. (3) Within one day after section of the phrenic nerve, the axon disintegrated and miniature end-plate potentials ceased to occur. Subsequently, miniature potentials were not observed at denervated end-plates, except during the third week after denervation, at which time a low-frequency discharge was seen in eight out of 770 fibres. The miniature potentials at these end-plates resembled those at normal junctions, and were presumably also due to acetylcholine acting on the muscle membrane. (4) The synaptic folds remain for several months after denervation, and serve to identify electron-microscopically the denervated end-plate. After prolonged denervation (> 3 weeks), when miniature end-plate potentials were never observed, there was generally no cell overlying the synaptic folds. (5) During the first 3 weeks after denervation, a nucleated cell, presumably the Schwann cell, was in close contact with the muscle. ‘Schwann-muscle' contacts were observed in muscle without miniature end-plate potentials. (6) Electron microscopy of a portion of denervated muscle, which included a fibre with miniature potentials, showed that the fibre had extensive ‘Schwann-muscle’ contacts. (7) It is concluded that the Schwann cell is the source of the packages of acetylcholine which evoke miniature end-plate potentials in denervated muscle. Since the Schwann cell was in contact with muscle fibres without miniature potentials, it appears that the presence of the Schwann cell is a necessary, but not a sufficient, condition for the production of miniature potentials at denervated end-plates.

scholarly journals Long-distance regulation of regenerating frog axons

1987 ◽  
Vol 132 (1) ◽  
pp. 151-160
Author(s):  
D. P. Kuffler
Keyword(s):  
Muscle Fibre ◽  
Basal Lamina ◽  
Chemical Signals ◽  
Regeneration Process ◽  
Muscle Fibres ◽  
Denervated Muscle ◽  
Long Distance ◽  
Nerve Crush ◽  
Distance Regulation ◽  
Molecular Signals

Following a nerve crush, damaged frog motor axons regenerate to reinnervate their denervated muscle fibre targets. The axons do this by growing down their old nerve tubes to their former synaptic sites. It is the naked basal lamina of the nerve tube that appears to direct the regenerating axons by providing a substratum over which the axons will preferentially grow. Another possible mechanism for directing the regenerating axons to the end-plates is the release of molecular signals by the cells of the nerve tube or by the denervated muscle fibres. This paper provides evidence that chemical signals do direct the regeneration process. Such signals, released several millimetres from a growing nerve tip, cause it to change direction and bend towards the source. Both the cells of the nerve tube and the denervated muscle fibres release diffusible substances and thereby establish a gradient that affects the regenerating axons.

scholarly journals Axonal regulation of Schwann cell integrin expression suggests a role for alpha 6 beta 4 in myelination.

1993 ◽  
Vol 123 (5) ◽  
pp. 1223-1236 ◽  
Author(s):  
S Einheber ◽  
T A Milner ◽  
F Giancotti ◽  
J L Salzer
Keyword(s):  
Schwann Cell ◽  
Schwann Cells ◽  
Basal Lamina ◽  
Cell Contact ◽  
Myelin Associated Glycoprotein ◽  
Dorsal Root Ganglia Neurons ◽  
Outer Plasma Membrane

Ensheathment and myelination of axons by Schwann cells in the peripheral nervous system requires contact with a basal lamina. The molecular mechanism(s) by which the basal lamina promotes myelination is not known but is likely to reflect the activity of integrins expressed by Schwann cells. To initiate studies on the role of integrins during myelination, we characterized the expression of two integrin subunits, beta 1 and beta 4, in an in vitro myelination system and compared their expression to that of the glial adhesion molecule, the myelin-associated glycoprotein (MAG). In the absence of neurons, Schwann cells express significant levels of beta 1 but virtually no beta 4 or MAG. When Schwann cells are cocultured with dorsal root ganglia neurons under conditions promoting myelination, expression of beta 4 and MAG increased dramatically in myelinating cells, whereas beta 1 levels remained essentially unchanged. (In general agreement with these findings, during peripheral nerve development in vivo, beta 4 levels also increase during the period of myelination in sharp contrast to beta 1 levels which show a striking decrease.) In cocultures of neurons and Schwann cells, beta 4 and MAG appear to colocalize in nascent myelin sheaths but have distinct distributions in mature sheaths, with beta 4 concentrated in the outer plasma membrane of the Schwann cell and MAG localized to the inner (periaxonal) membrane. Surprisingly, beta 4 is also present at high levels with MAG in Schmidt-Lanterman incisures. Immunoprecipitation studies demonstrated that primary Schwann cells express beta 1 in association with the alpha 1 and alpha 6 subunits, while myelinating Schwann cells express alpha 6 beta 4 and possibly alpha 1 beta 1. beta 4 is also downregulated during Wallerian degeneration in vitro, indicating that its expression requires continuous Schwann cell contact with the axon. These results indicate that axonal contact induces the expression of beta 4 during Schwann cell myelination and suggest that alpha 6 beta 4 is an important mediator of the interactions of myelinating Schwann cells with the basal lamina.

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