The Fine Structure and Morphological Organization of the Peripheral Nerve-fibres and Trunks of the Cockroach (Periplaneta americana)

1958 ◽  
Vol s3-99 (47) ◽  
pp. 333-340
Author(s):  
ARTHUR HESS
Keyword(s):  
Cell Membrane ◽  
Schwann Cell ◽  
Peripheral Nerve ◽  
Schwann Cells ◽  
Myelin Sheath ◽  
Plasma Membranes ◽  
Periplaneta Americana ◽  
Nerve Trunk ◽  
Bromphenol Blue ◽  
Nerve Fibres

Sections of the peripheral nerve-trunks of the metathoracic leg of the cockroach (Periplaneta americana) were studied with the electron microscope. Paraffin sections were also prepared and stained. Protargol succeeds in staining the nerve-fibres. Osmium tetroxide, a modified Weigert procedure, and Luxol fast blue stain the myelin sheaths, as does mercuric bromphenol blue, a protein stain. The axoplasm is relatively free of formed elements; it contains mitochondria. The myelin sheath, when present on the largest and also some smaller fibres, consists of about two or three loose over lapping processes of Schwann cells, covered by their plasma membranes, enclosing lipid-like droplets and having a beaded appearance. Between the nerve-fibres in the nerve-trunk is Schwann-cell cytoplasm, which arises from Schwann cells that surround the whole nerve-trunk. The same fold of Schwann-cell membrane may enter into the formation of the myelin sheath around more than one nerve-fibre. Several small non-myelinated fibres, which may be as small as 0.3 µ in diameter or less, may be enclosed in the same fold of Schwann-cell membrane. Outside of the Schwann-cell layer and surrounding the nerve-trunk is a thin layer of connective tissue, which does not send trabeculae into the interior of the nerve. Tracheae and tracheoles accompany the nerve but are not included within the sheaths surrounding a nerve-trunk, even near the termination of the nerve-fibres in muscle. The structure of the cockroach peripheral nerve is compared with that described by previous investigators, with that of other insects, and with invertebrate and vertebrate nerve.

The fine structure and morphological organization of non-myelinated nerve fibres

1956 ◽  
Vol 144 (917) ◽  
pp. 496-506 ◽  
Keyword(s):  
Fine Structure ◽  
Schwann Cell ◽  
Peripheral Nerve ◽  
Schwann Cells ◽  
Myelin Sheath ◽  
Peripheral Nerves ◽  
Nerve Fibres ◽  
Myelinated Nerve ◽  
Morphological Organization ◽  
Myelinated Fibres

The fine structure and morphological organization of non-myelinated nerve fibres were studied by ultra-thin sectioning and electron microscopy in peripheral nerves, autonomic nerves and dorsal roots. Several non-myelinated fibres share the cytoplasm of a Schwann cell. The Schwann cells of non-myelinated fibres form a syncytium. The fibres are incompletely sur­rounded by Schwann cell cytoplasm and are suspended in the cytoplasm by mesaxons formed by the plasma membranes of the Schwann cell. The various relationships of mesaxon and nerve fibre are described. Non-myelinated fibres which do not share a Schwann cell are seen very frequently in the sciatic nerve of a new-born mouse but become less common as myelination proceeds and are rare in adults. It is therefore suggested that in developing peripheral nerves, the non­ myelinated fibres that are destined to myelinate are not organized into groups within a single Schwann cell, even before their myelin sheath has appeared; they are, at least for the ages examined here, individuals in relation to a surrounding individual Schwann cell. It is also suggested that the non-myelinated fibres that will never acquire a myelin sheath are organized in a developing peripheral nerve in the same manner as in the adult nerve—several fibres sharing a single Schwann cell that is part of a syncytial system of Schwann cells. Thus, in a developing peripheral nerve, it appears that two types of non-myelinated fibres are present—one destined to myelinate and lying alone in its own Schwann cell and the other, destined to remain unmyelinated and sharing, along with other non-myelinated fibres of the same type, a Schwann cell. The significance of these observations is discussed in relation to the development of nerve fibres and possible physiological importance.

Schwann Cell Reactions in Acute and Chronic Segmental Demyelinating Neuropathies

1968 ◽  
Vol 26 ◽  
pp. 108-109
Author(s):  
Roy O. Weller
Keyword(s):  
Schwann Cell ◽  
Peripheral Nerve ◽  
Schwann Cells ◽  
Myelin Sheath ◽  
Wallerian Degeneration ◽  
Demyelinating Disease ◽  
Segmental Demyelination ◽  
Recovery Stage ◽  
Myelin Sheaths ◽  
Demyelinating Neuropathies

The length of axon that each Schwann cell myelinates in a normal peripheral nerve is approximately proportional to the diameter of the axon and the thickness of the myelin sheath produced. When segmental demyelination occurs, individual segments, represented by the length of axon covered by one Schwann cell, lose their myelin sheaths but the axons are preserved. This differs from Wallerian degeneration where myelin destruction occurs along the length of a nerve fibre following death of the axon.In experimental diphtheritic neuropathy, an acute segmental demyelinating disease, lysosomes accumulate within the Schwann cells prior to disruption of the myelin sheath; furthermore, the site of initial myelin breakdown appears to be closely related to the collections of lysosomes. The Schwann cell starts to form a new myelin sheath around the axon probably within a few hours of the destruction of the original myelin sheath, and while the latter is being catabolised within lysosomal vacuoles This stage of remyelination follows a similar course to primary myelination, so that the recovery stage is characterised by normal axons with either no myelin, or surrounded by sheaths that are very thin relative to the diameter of the axon.

The Distribution of Electron-Dense Tracers in Peripheral Nerve Fibres

1971 ◽  
Vol 8 (2) ◽  
pp. 541-555
Author(s):  
SUSAN M. HALL ◽  
P. L. WILLIAMS
Keyword(s):  
Schwann Cell ◽  
Peripheral Nerve ◽  
Myelin Sheath ◽  
External Surface ◽  
Nerve Fibres ◽  
Cell Cytoplasm ◽  
Line Region ◽  
Periaxonal Space

Two electron-dense tracers, ferritin and lanthanum, have been administered to peripheral nerve fibres, and their uptake has been studied ultrastructurally. It was found that the perineurium was an effective barrier to ferritin in vivo, and the tracer was subsequently injected sub-perineurially. Ferritin uptake over a 120-min period was confined to occasional phagocytic vesicles in perineurial and Schwann cells, and to the nodal gap substance and paranodal periaxonal space. No uptake was observed in the myelin sheath, incisural intraperiod line gap, or in the axoplasm. Soaking fibres in ferritin in vitro resulted in a more generalized cytoplasmic and axoplasmic uptake, although the myelin sheath and Schmidt-Lanterman incisures remained devoid of the tracer. Lanthanum nitrate, included in the fixative solution, delineated the patent incisural intraperiod line gap, and outlined the external surface of the terminal loops of nodal Schwann cell cytoplasm, and the paranodal Schwann cell-axolemmal junction. Unlike ferritin, La3+ penetrated the myelin sheath, being usually confined to the intraperiod line region of the outer lamellae, where it was associated with a widening of the lamellar unit, and an apparent splitting of the intraperiod line. The results are discussed with regard to distribution of extracellular space in peripheral nerve fibres.

Periaxin expression in myelinating Schwann cells: modulation by axon-glial interactions and polarized localization during development

Development ◽  
1995 ◽  
Vol 121 (12) ◽  
pp. 4265-4273 ◽  
Author(s):  
S.S. Scherer ◽  
Y.T. Xu ◽  
P.G. Bannerman ◽  
D.L. Sherman ◽  
P.J. Brophy
Keyword(s):  
Cell Membrane ◽  
Membrane Protein ◽  
Schwann Cell ◽  
Schwann Cells ◽  
Protein Interactions ◽  
Myelin Sheath ◽  
Myelin Proteins ◽  
Developmentally Regulated ◽  
Protein Levels ◽  
Myelin Sheaths

Periaxin is a newly described protein that is expressed exclusively by myelinating Schwann cells. In developing nerves, periaxin is first detected as Schwann cells ensheathe axons, prior to the appearance of the proteins that characterize the myelin sheath. Periaxin is initially concentrated in the adaxonal membrane (apposing the axon) but, during development, as myelin sheaths mature, periaxin becomes predominately localized at the abaxonal Schwann cell membrane (apposing the basal lamina). In permanently axotomized adult nerves, periaxin is lost from the abaxonal and adaxonal membranes, becomes associated with degenerating myelin sheaths and is phagocytosed by macrophages. In crushed nerves, in which axons regenerate and are remyelinated, periaxin is first detected in the adoxonal membrane as Schwann cells ensheathe regenerating axons, but again prior to the appearance of other myelin proteins. Periaxin mRNA and protein levels change in parallel with those of other myelin-related genes after permanent axotomy and crush. These data demonstrate that periaxin is expressed by myelinating Schwann cells in a dynamic, developmentally regulated manner. The shift in localization of periaxin in the Schwann cell after completion of the spiralization phase of myelination suggests that periaxin participates in membrane-protein interactions that are required to stabilize the mature myelin sheath.

scholarly journals Axon-dependent expression of YAP/TAZ mediates Schwann cell remyelination but not proliferation after nerve injury

2019 ◽  
Author(s):  
Matthew Grove ◽  
Hyunkyoung Lee ◽  
Huaqing Zhao ◽  
Young-Jin Son
Keyword(s):  
Schwann Cell ◽  
Peripheral Nerve ◽  
Schwann Cells ◽  
Nerve Injury ◽  
Myelin Sheath ◽  
Transcriptional Activity ◽  
Axon Degeneration ◽  
Adult Mice ◽  
Functional Regeneration ◽  
Growth Promoting

ABSTRACTPreviously we showed that YAP/TAZ promote not only proliferation but also differentiation of immature Schwann cells (SCs), thereby forming and maintaining the myelin sheath around peripheral axons (Grove et al., 2017). Here we show that YAP/TAZ are required for mature SCs to restore peripheral myelination, but not to proliferate, after nerve injury. We find that YAP/TAZ dramatically disappear from SCs of adult mice concurrent with axon degeneration after nerve injury. They reappear in SCs only if axons regenerate. YAP/TAZ ablation does not impair SC proliferation or transdifferentiation into growth promoting repair SCs. SCs lacking YAP/TAZ, however, fail to upregulate myelin-associated genes and completely fail to remyelinate regenerated axons. We also show that both YAP and TAZ are redundantly required for optimal remyelination. These findings suggest that axons regulate transcriptional activity of YAP/TAZ in adult SCs and that YAP/TAZ are essential for functional regeneration of peripheral nerve.

The in Vivo and Ultrastructural Effects of Injection of Lysophosphatidyl Choline into Myelinated Peripheral Nerve Fibres of the Adult Mouse

1971 ◽  
Vol 9 (3) ◽  
pp. 769-789
Author(s):  
SUSAN M. HALL ◽  
N. A. GREGSON
Keyword(s):  
Schwann Cell ◽  
Peripheral Nerve ◽  
Myelin Sheath ◽  
Time Course ◽  
Adult Mouse ◽  
Phospholipase A ◽  
Nerve Fibres ◽  
Lysophosphatidyl Choline

The action of phospholipase A and lysophosphatidyl choline (LPC) on mature, myelinated peripheral nerve fibres has been studied in vivo and electron microscopically, following sub-perineurial injection of these substances. Within 30 min, demyelination was observed in vivo along cylindrico-conical segments, spreading from Schmidt-Lanterman incisures and nodes of Ranvier. By 96 h, all traces of the myelin sheath had disappeared from the area of the lesion, and had been replaced by debris-laden cells lying in chains parallel to one another and the long axis of the fibre. During the next few weeks these cells gradually disappeared, and numerous finely myelinated axons, running between, and in continuity with, the normal fibres proximal and distal to the lesion were observed. If lower concentrations of LPC were used the number of fibres involved decreased, although the demyelinative changes followed the same time-course. Ultrastructurally, demyelination involved progressive disruption and removal of the lamellar sheath, observed initially as a splitting of the intraperiod line within 30 min. Subsequent breakdown resulted in the formation of strands of 4-6 nm repeat material which was further degraded through quintuple- and triple-layered lamellar units to foam-like systems of disorganized lamellar fragments. The Schwann cell and axons appeared to be undamaged by phospholipase A and LPC, and retained their normal impermeability to exogenous ferritin. The significance of the demyelinating capacity of LPC in vivo is discussed in terms of its known action on myelin in vitro, the rapidity and apparent specificity of its action demonstrated in this study, and its potential involvement in pathological demyelination.

scholarly journals Axon-dependent expression of YAP/TAZ mediates Schwann cell remyelination but not proliferation after nerve injury

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Matthew Grove ◽  
Hyunkyoung Lee ◽  
Huaqing Zhao ◽  
Young-Jin Son
Keyword(s):  
Schwann Cell ◽  
Peripheral Nerve ◽  
Schwann Cells ◽  
Nerve Injury ◽  
Myelin Sheath ◽  
Transcriptional Activity ◽  
Axon Degeneration ◽  
Adult Mice ◽  
Functional Regeneration ◽  
Growth Promoting

Previously we showed that YAP/TAZ promote not only proliferation but also differentiation of immature Schwann cells (SCs), thereby forming and maintaining the myelin sheath around peripheral axons (Grove et al., 2017). Here we show that YAP/TAZ are required for mature SCs to restore peripheral myelination, but not to proliferate, after nerve injury. We find that YAP/TAZ dramatically disappear from SCs of adult mice concurrent with axon degeneration after nerve injury. They reappear in SCs only if axons regenerate. YAP/TAZ ablation does not impair SC proliferation or transdifferentiation into growth promoting repair SCs. SCs lacking YAP/TAZ, however, fail to upregulate myelin-associated genes and completely fail to remyelinate regenerated axons. We also show that both YAP and TAZ are redundantly required for optimal remyelination. These findings suggest that axons regulate transcriptional activity of YAP/TAZ in adult SCs and that YAP/TAZ are essential for functional regeneration of peripheral nerve.

scholarly journals Transposon Mutagenesis-Guided CRISPR/Cas9 Screening Strongly Implicates Dysregulation of Hippo/YAP Signaling in Malignant Peripheral Nerve Sheath Tumor Development

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1584
Author(s):  
Germán L. Vélez-Reyes ◽  
Nicholas Koes ◽  
Ji Hae Ryu ◽  
Gabriel Kaufmann ◽  
Mariah Berner ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Schwann Cell ◽  
Peripheral Nerve ◽  
Cell Line ◽  
Schwann Cells ◽  
Tumor Suppressor Genes ◽  
Tumor Formation ◽  
Loss Of Function ◽  
Suppressor Genes ◽  
Nerve Sheath

Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive, genomically complex, have soft tissue sarcomas, and are derived from the Schwann cell lineage. Patients with neurofibromatosis type 1 syndrome (NF1), an autosomal dominant tumor predisposition syndrome, are at a high risk for MPNSTs, which usually develop from pre-existing benign Schwann cell tumors called plexiform neurofibromas. NF1 is characterized by loss-of-function mutations in the NF1 gene, which encode neurofibromin, a Ras GTPase activating protein (GAP) and negative regulator of RasGTP-dependent signaling. In addition to bi-allelic loss of NF1, other known tumor suppressor genes include TP53, CDKN2A, SUZ12, and EED, all of which are often inactivated in the process of MPNST growth. A sleeping beauty (SB) transposon-based genetic screen for high-grade Schwann cell tumors in mice, and comparative genomics, implicated Wnt/β-catenin, PI3K-AKT-mTOR, and other pathways in MPNST development and progression. We endeavored to more systematically test genes and pathways implicated by our SB screen in mice, i.e., in a human immortalized Schwann cell-based model and a human MPNST cell line, using CRISPR/Cas9 technology. We individually induced loss-of-function mutations in 103 tumor suppressor genes (TSG) and oncogene candidates. We assessed anchorage-independent growth, transwell migration, and for a subset of genes, tumor formation in vivo. When tested in a loss-of-function fashion, about 60% of all TSG candidates resulted in the transformation of immortalized human Schwann cells, whereas 30% of oncogene candidates resulted in growth arrest in a MPNST cell line. Individual loss-of-function mutations in the TAOK1, GDI2, NF1, and APC genes resulted in transformation of immortalized human Schwann cells and tumor formation in a xenograft model. Moreover, the loss of all four of these genes resulted in activation of Hippo/Yes Activated Protein (YAP) signaling. By combining SB transposon mutagenesis and CRISPR/Cas9 screening, we established a useful pipeline for the validation of MPNST pathways and genes. Our results suggest that the functional genetic landscape of human MPNST is complex and implicate the Hippo/YAP pathway in the transformation of neurofibromas. It is thus imperative to functionally validate individual cancer genes and pathways using human cell-based models, to determinate their role in different stages of MPNST development, growth, and/or metastasis.

scholarly journals Interleukin-4 Regulates the Expression of CD209 and Subsequent Uptake of Mycobacterium leprae by Schwann Cells in Human Leprosy

2010 ◽  
Vol 78 (11) ◽  
pp. 4634-4643 ◽  
Author(s):  
Rosane M. B. Teles ◽  
Stephan R. Krutzik ◽  
Maria T. Ochoa ◽  
Rosane B. Oliveira ◽  
Euzenir N. Sarno ◽  
...  
Keyword(s):  
Schwann Cell ◽  
Peripheral Nerve ◽  
Schwann Cells ◽  
Primary Cultures ◽  
Mycobacterium Leprae ◽  
Microbial Pathogens ◽  
Interleukin 4 ◽  
Common Mechanism ◽  
Specific Cell

ABSTRACT The ability of microbial pathogens to target specific cell types is a key aspect of the pathogenesis of infectious disease. Mycobacterium leprae, by infecting Schwann cells, contributes to nerve injury in patients with leprosy. Here, we investigated mechanisms of host-pathogen interaction in the peripheral nerve lesions of leprosy. We found that the expression of the C-type lectin, CD209, known to be expressed on tissue macrophages and to mediate the uptake of M. leprae, was present on Schwann cells, colocalizing with the Schwann cell marker, CNPase (2′,3′-cyclic nucleotide 3′-phosphodiesterase), along with the M. leprae antigen PGL-1 in the peripheral nerve biopsy specimens. In vitro, human CD209-positive Schwann cells, both from primary cultures and a long-term line, have a higher binding of M. leprae compared to CD209-negative Schwann cells. Interleukin-4, known to be expressed in skin lesions from multibacillary patients, increased CD209 expression on human Schwann cells and subsequent Schwann cell binding to M. leprae, whereas Th1 cytokines did not induce CD209 expression on these cells. Therefore, the regulated expression of CD209 represents a common mechanism by which Schwann cells and macrophages bind and take up M. leprae, contributing to the pathogenesis of leprosy.

scholarly journals Dependence on Schwann Cell-Derived Laminin-γ1 Differentiates Early Lymphoid and Myeloid Development

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 37-37
Author(s):  
Kristin Komnick ◽  
Jennifer May ◽  
Pouneh Kermani ◽  
Sreemanti Basu ◽  
Irene Hernandez ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Nervous System ◽  
Schwann Cell ◽  
Peripheral Nerve ◽  
Peripheral Nervous System ◽  
Schwann Cells ◽  
Adrenergic Nerve ◽  
Spleen Size ◽  
Mouse Line ◽  
Myeloid Development

Blood cell production is regulated by peripheral nerve fibers that innervate the bone marrow. However, little is known about the development or maintenance of hematopoietic innervation. Schwann cells (SCs) are the primary axon 'support cells' of the peripheral nervous system (PNS), and abnormal SC development is sufficient to impair peripheral nerve function. SCs are also the primary repair cell for the PNS which makes them an attractive therapeutic target for normalization of drug or malignancy-induced 'hematopoietic neuropathy'. We hypothesized that neural regulation of hematopoiesis is dependent on SC development. To test this hypothesis, we used the Myelin Protein Zero-Cre (MP0-Cre); Lamc1fl/fl mouse line in which laminin-γ1 expression is deleted from SC precursors and their progeny1. Early SC maturation is dependent on autocrine SC precursor-derived molecules such as laminin-γ1. SC differentiation arrests prior to axon sorting and ensheathment in MP0-Cre; Lamc1fl/fl mice, and causes a global peripheral neuropathy that persists throughout the lifetime of the animal. Preliminary hematopoietic analysis of 'steady state' MP0-Cre; Lamc1fl/fl and littermate control mice has shown the following: (1) MP0-Cre; Lamc1fl/fl bone marrow is innervated, and Cre-mediated gene recombination occurs in cells immunophenotypically consistent with SCs throughout the peripheral nervous system, including those in the bone marrow; (2) MP0-Cre; Lamc1fl/fl mice are lymphopenic but not neutropenic; (3) MP0-Cre; Lamc1fl/fl mice have significantly reduced spleen size and cellularity; and (4) MP0-Cre; Lamc1fl/fl bone marrow has an ~50% reduction in Lin-Sca-1+Kit+(LSK) cells (measured as a percentage of the Lin- compartment of the bone marrow). These results are consistent with earlier work by our groups in which we found that global Lamc1 gene deletion in adult mice induced peripheral blood lymphopenia, reduced spleen size, and a niche-dependent reduction of lymphoid progenitor and precursor cells that was secondary to increased lymphoid precursor cell apoptosis and reduced proliferation (UBC-CreERT2; Lamc1fl/fl mouse line). As with the SC-specific laminin-γ1 deficient mice, myelopoiesis was preserved in the UBC-CreERT2; Lamc1fl/fl mice. Based on results from MP0-Cre; Lamc1fl/fl and UBC-CreERT2; Lamc1fl/fl mice, we conclude that early lymphoid but not myeloid development requires laminin-γ1 expression by MP0-Cre-targetted niche cells, i.e. Schwann Cells. Our results are consistent with reports from other labs that hematopoietic sympathetic neuropathy promotes aberrant myeloid expansion at the expense of lymphopoiesis2. Going forward, we will determine whether lymphopoietic development is dependent on global versus laminin-specific SC-derived cues, and whether these signals are transmitted directly between SCs and lymphoid biased HSPCs or indirectly via other components of the hematopoietic niche. We anticipate that this line of investigation will provide molecular insights and pharmacologic targets for prevention and or normalization of the 'hematopoietic neuropathy' induced by diabetes, aging, neurotoxic chemotherapies and myeloid malignancies. REFERENCES: 1 Yu, W. M., Feltri, M. L., Wrabetz, L., Strickland, S. & Chen, Z. L. Schwann cell-specific ablation of laminin gamma1 causes apoptosis and prevents proliferation. J Neurosci25, 4463-4472, doi:10.1523/JNEUROSCI.5032-04.2005 (2005). 2 Maryanovich, M. et al. Adrenergic nerve degeneration in bone marrow drives aging of the hematopoietic stem cell niche. Nat Med24, 782-791, doi:10.1038/s41591-018-0030-x (2018). Disclosures No relevant conflicts of interest to declare.

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