scholarly journals Division of Labor of Schwann Cell Integrins during Migration on Peripheral Nerve Extracellular Matrix Ligands

1997 ◽  
Vol 185 (2) ◽  
pp. 215-228 ◽  
Author(s):  
Richard Milner ◽  
Martin Wilby ◽  
Stephen Nishimura ◽  
Kevin Boylen ◽  
Gwynneth Edwards ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Schwann Cell ◽  
Peripheral Nerve ◽  
Division Of Labor

Beta 4 integrin expression in myelinating Schwann cells is polarized, developmentally regulated and axonally dependent

Development ◽  
1994 ◽  
Vol 120 (5) ◽  
pp. 1287-1301 ◽  
Author(s):  
M.L. Feltri ◽  
S.S. Scherer ◽  
R. Nemni ◽  
J. Kamholz ◽  
H. Vogelbacker ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Schwann Cell ◽  
Peripheral Nerve ◽  
Schwann Cells ◽  
Morphological Changes ◽  
Cell Phenotype ◽  
Integrin Subunit ◽  
Integrin Expression ◽  
Cultured Schwann Cells ◽  
Mediate Cell

In developing and regenerating peripheral nerve, Schwann cells interact with axons and extracellular matrix in order to ensheath and myelinate axons. Both of these interactions are likely to be mediated by adhesion molecules, including integrins, which mediate cell-cell and cell-extracellular matrix interactions. Recently, the beta 4 integrin subunit was reported to be expressed by Schwann cells in peripheral nerve. We have examined the expression of beta 4, beta 1 and their common heterodimeric partner, the alpha 6 integrin subunit, in developing and regenerating rat peripheral nerve. beta 4 and alpha 6 are enriched in peripheral nerve and they co-localize at the abaxonal surface of myelinating Schwann cells, opposite the Schwann cell basal lamina, which contains possible ligands of alpha 6 beta 4. In contrast, beta 4 and alpha 6 are expressed in a different pattern in non-myelinating Schwann cells. The level of beta 4, but not alpha 6 or beta 1 mRNAs, increases progressively in developing nerves, reaching a peak in adult nerves well after the peak of the myelin-specific mRNAs. After axotomy, the expression of beta 4 mRNA and protein, but not alpha 6 or beta 1 mRNAs, fall rapidly but subsequently are reinduced by regenerating axons. Similarly, in cultured Schwann cells, the expression of beta 4 mRNA, but not alpha 6 mRNA, is significantly modulated by forskolin, a drug that elevates cAMP and mimics some of the effects of axonal contact. beta 4 integrin expression in Schwann cells, therefore, is regulated by Schwann cell-axon interactions, which are known to be critical in determining the Schwann cell phenotype. Furthermore, the polarized expression of alpha 6 beta 4 to the abaxonal surface of myelinating Schwann cells suggests that alpha 6 beta 4 may mediate in part the morphological changes required of Schwann cells in the process of myelination in the peripheral nervous system.

Regulation of expression of fibronectin and its receptor, alpha 5 beta 1, during development and regeneration of peripheral nerve

Development ◽  
1992 ◽  
Vol 116 (3) ◽  
pp. 767-782 ◽  
Author(s):  
F. Lefcort ◽  
K. Venstrom ◽  
J.A. McDonald ◽  
L.F. Reichardt
Keyword(s):  
Extracellular Matrix ◽  
Cell Migration ◽  
Schwann Cell ◽  
Peripheral Nerve ◽  
Integrin Receptor ◽  
Regulation Of Expression ◽  
Receptor Alpha ◽  
Peripheral Neurons ◽  
Schwann Cell Migration ◽  
Regenerating Nerve

The extracellular matrix glycoprotein, fibronectin, is a potent promoter of peripheral neurite outgrowth. Interactions of peripheral neurons with fibronectin have been shown to be primarily mediated by the beta 1 class of integrin heterodimers. In the present study, we have examined the expression and regulation of fibronectin and its integrin receptor, alpha 5 beta 1, in developing and regenerating chick peripheral nerve. We show that fibronectin and alpha 5 beta 1 are expressed at comparatively high levels in developing nerve with alpha 5 beta 1 expression on axons and non-neuronal cells. With nerve maturation, both proteins are less prominently expressed and the cellular pattern of alpha 5 beta 1 expression becomes more restricted. Following lesion of mature nerve, both fibronectin and alpha 5 beta 1 are strongly induced with prominent expression of alpha 5 beta 1 on regenerating neurites and Schwann cells. The elevation in fibronectin levels in the regenerating nerve is highest in the vicinity of the lesion, an area undergoing extensive cellular remodeling including Schwann cell migration and growth cone extension. Our results suggest that fibronectin and its receptor, alpha 5 beta 1, may mediate functionally important interactions in the development and regeneration of peripheral nerve.

Role of Peripheral Nerve Extracellular Matrix in Schwann Cell Function and in Neurite Regeneration

1989 ◽  
Vol 11 (4-5) ◽  
pp. 348-360 ◽  
Author(s):  
Mary Bartlett Bunge ◽  
Richard P. Bunge ◽  
Naomi Kleitman ◽  
Andy C. Dean
Keyword(s):  
Extracellular Matrix ◽  
Schwann Cell ◽  
Peripheral Nerve ◽  
Cell Function

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 Cyclic tensile stimulation enrichment of Schwann cell-laden auxetic hydrogel scaffolds towards peripheral nerve tissue engineering

2020 ◽  
Vol 195 ◽  
pp. 108982 ◽  
Author(s):  
Yi-Wen Chen ◽  
Kan Wang ◽  
Chia-Che Ho ◽  
Chia-Tze Kao ◽  
Hooi Yee Ng ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Schwann Cell ◽  
Peripheral Nerve ◽  
Nerve Tissue ◽  
Hydrogel Scaffolds ◽  
Nerve Tissue Engineering

Activated Schwann Cell-Like Cells on Aligned Fibrin-Poly(Lactic-Co-Glycolic Acid) Structures: A Novel Construct for Application in Peripheral Nerve Regeneration

2014 ◽  
Vol 200 (5) ◽  
pp. 287-299 ◽  
Author(s):  
Christina M.A.P. Schuh ◽  
Tatjana J. Morton ◽  
Asmita Banerjee ◽  
Christian Grasl ◽  
Heinrich Schima ◽  
...  
Keyword(s):  
Schwann Cell ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Glycolic Acid ◽  
Peripheral Nerve Regeneration

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.

Sign in / Sign up

Export Citation Format

Share Document