scholarly journals Unravelling crucial biomechanical resilience of myelinated peripheral nerve fibres provided by the Schwann cell basal lamina and PMP22

2014 ◽  
Vol 4 (1) ◽  
Author(s):  
Gonzalo Rosso ◽  
Ivan Liashkovich ◽  
Burkhard Gess ◽  
Peter Young ◽  
Alejandra Kun ◽  
...  
Keyword(s):  
Schwann Cell ◽  
Peripheral Nerve ◽  
Basal Lamina ◽  
Nerve Fibres

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.

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.

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.

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 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.

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