Axons regulate Schwann cell expression of the major myelin and NGF receptor genes

Development ◽  
1988 ◽  
Vol 102 (3) ◽  
pp. 499-504 ◽  
Author(s):  
G. Lemke ◽  
M. Chao
Keyword(s):  
Schwann Cell ◽  
Schwann Cells ◽  
Growth Factor Receptor ◽  
Myelin Proteins ◽  
Ngf Receptor ◽  
Genes Encoding ◽  
Messenger System ◽  
High Level ◽  
Cell Expression ◽  
Inductive Signal

The elaboration of myelin by Schwann cells is triggered by contact with appropriate peripheral axons. Among the most prominent features of this interaction is the activation and high-level expression of the genes encoding the major myelin proteins P0 and Myelin Basic Protein (MBP). Although the initial induction of these genes is thought to be dependent upon contact with axons, neither the inductive signal of the axon nor the receptor and associated second messenger system of the Schwann cell that transduces this signal has been identified. In this report, we demonstrate that expression of the P0 and MBP genes in rapidly myelinating Schwann cells is sharply reduced upon withdrawal of axons, but that this expression can be substantially restored by agents that raise the intracellular concentration of cyclic AMP. We further show that Schwann cell expression of a third gene, i.e. that encoding the Nerve Growth Factor receptor, is strongly activated by the withdrawal of axons, and that this activation is largely independent of cAMP.

Remyelination of Demyelinated CNS Axons by Transplanted Human Schwann Cells: The Deleterious Effect of Contaminating Fibroblasts

2001 ◽  
Vol 10 (3) ◽  
pp. 305-315 ◽  
Author(s):  
C. M. H. Brierley ◽  
A. J. Crang ◽  
Y. Iwashita ◽  
J. M. Gilson ◽  
N. J. Scolding ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Schwann Cell ◽  
Schwann Cells ◽  
Axonal Degeneration ◽  
Autologous Transplantation ◽  
Growth Factor Receptor ◽  
Adult Rats ◽  
Demyelinating Lesions ◽  
Cell Implantation

Areas of demyelination can be remyelinated by transplanting myelin-forming cells. Schwann cells are the naturally remyelinating cells of the peripheral nervous system and have a number of features that may make them attractive for cell implantation therapies in multiple sclerosis, in which spontaneous but limited Schwann cell remyelination has been well documented. Schwann cells can be expanded in vitro, potentially affording the opportunity of autologous transplantation; and they might also be spared the demyelinating process in multiple sclerosis. Although rat, cat, and monkey Schwann cells have been transplanted into rodent demyelinating lesions, the behavior of transplanted human Schwann cells has not been evaluated. In this study we examined the consequences of injecting human Schwann cells into areas of acute demyelination in the spinal cords of adult rats. We found that transplants containing significant fibroblast contamination resulted in deposition of large amounts of collagen and extensive axonal degeneration. However, Schwann cell preparations that had been purified by positive immunoselection using antibodies to human low-affinity nerve growth factor receptor containing less than 10% fibroblasts were associated with remyelination. This result indicates that fibroblast contamination of human Schwann cells represents a greater problem than would have been appreciated from previous studies.

The effects of embryonic retinal neurons on neural crest cell differentiation into Schwann cells

Development ◽  
1990 ◽  
Vol 109 (4) ◽  
pp. 925-934 ◽  
Author(s):  
L.C. Smith-Thomas ◽  
A.R. Johnson ◽  
J.W. Fawcett
Keyword(s):  
Schwann Cell ◽  
Neural Crest ◽  
Schwann Cells ◽  
Neural Crest Cell ◽  
Neural Crest Cells ◽  
Cell Types ◽  
Cell Markers ◽  
Ngf Receptor ◽  
S 100 ◽  
The Many

Amongst the many cell types that differentiate from migratory neural crest cells are the Schwann cells of the peripheral nervous system. While it has been demonstrated that Schwann cells will not fully differentiate unless in contact with neurons, the factors that cause neural crest cells to enter the differentiative pathway that leads to Schwann cells are unknown. In a previous paper (Development 105: 251, 1989), we have demonstrated that a proportion of morphologically undifferentiated neural crest cells express the Schwann cell markers 217c and NGF receptor, and later, as they acquire the bipolar morphology typical of Schwann cells in culture, express S-100 and laminin. In the present study, we have grown axons from embryonic retina on neural crest cultures to see whether this has an effect on the differentiation of neural crest cells into Schwann cells. After 4 to 6 days of co-culture, many more cells had acquired bipolar morphology and S-100 staining than in controls with no retinal explant, and most of these cells were within 200 microns of an axon, though not necessarily in contact with axons. However, the number of cells expressing the earliest Schwann cell markers 217c and NGF receptor was not affected by the presence of axons. We conclude that axons produce a factor, which is probably diffusible, and which makes immature Schwann cells differentiate. The factor does not, however, influence the entry of neural crest cells into the earliest stages of the Schwann cell differentiative pathway.

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 Schwann cell expression of an oligodendrocyte-like remyelinating pattern after ethidium bromide injection in the rat spinal cord

2010 ◽  
Vol 68 (5) ◽  
pp. 783-787 ◽  
Author(s):  
Eduardo Fernandes Bondan ◽  
Maria Anete Lallo ◽  
Maria de Fátima Monteiro Martins ◽  
Dominguita Luhers Graça
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Schwann Cell ◽  
Schwann Cells ◽  
Ethidium Bromide ◽  
Rat Spinal Cord ◽  
Primary Demyelination ◽  
The Central Nervous System ◽  
Cell Expression

Schwann cells are recognized by their capacity of producing single internodes of myelin around axons of the peripheral nervous system. In the ethidium bromide (EB) model of primary demyelination in the brainstem, it is observed the entry of Schwann cells into the central nervous system in order to contribute to the myelin repair performed by the oligodendrocytes that survived to the EB gliotoxic action, being able to even remyelinate more than one axon at the same time, in a pattern of repair similar to the oligodendroglial one. The present study was developed in the spinal cord to observe if Schwann cells maintained this competence of attending simultaneously different internodes. It was noted that, on the contrary of the brainstem, Schwann cells were the most important myelinogenic cells in the demyelinated site and, although rare, also presented the capacity of producing more than one internode of myelin in distinct axons.

scholarly journals Understanding the mechanisms of entrapment neuropathies

2009 ◽  
Vol 26 (2) ◽  
pp. E7 ◽  
Author(s):  
Khoa Pham ◽  
Ranjan Gupta
Keyword(s):  
Schwann Cell ◽  
Schwann Cells ◽  
Axonal Injury ◽  
Reciprocal Relationship ◽  
Nerve Compression ◽  
Nerve Tissue ◽  
Myelin Proteins ◽  
Mechanical Stimuli ◽  
Entrapment Neuropathies ◽  
Chronic Nerve Compression

Compression neuropathies are highly prevalent, debilitating conditions with variable functional recovery following surgical decompression. Due to the limited amount of human nerve tissue available for analysis, a number of animal models have been created to help investigators understand the molecular and cellular pathogenesis of chronic nerve compression (CNC) injury. Evidence suggests that CNC injury induces concurrent Schwann cell proliferation and apoptosis in the early stages of the disorder. These proliferating Schwann cells downregulate myelin proteins, leading to local demyelination and remyelination in the region of injury. In addition, the downregulation of myelin proteins, in particular myelin-associated glycoprotein, allows for axonal sprouting. Interestingly, these changes occur in the absence of both morphological and electrophysiological evidence of axonal damage. This is in direct contrast to acute injuries, such as transection or crush, which are characterized by axonal injury followed by Wallerian degeneration. Because the accepted trigger for Schwann cell dedifferentiation is axonal injury, an alternate mechanism for Schwann response must exist in CNC injury. In vitro studies of pure Schwann cells have shown that these cells can respond directly to mechanical stimuli by downregulating myelin proteins and proliferating. These studies suggest that although the reciprocal relationship between neurons and glial cells is maintained, chronic nerve compression injury is a Schwann cell-mediated disease.

Krox-20 controls SCIP expression, cell cycle exit and susceptibility to apoptosis in developing myelinating Schwann cells

Development ◽  
1999 ◽  
Vol 126 (7) ◽  
pp. 1397-1406 ◽  
Author(s):  
T.S. Zorick ◽  
D.E. Syroid ◽  
A. Brown ◽  
T. Gridley ◽  
G. Lemke
Keyword(s):  
Schwann Cell ◽  
Schwann Cells ◽  
Cell Phenotype ◽  
Mouse Mutants ◽  
Morphological Criteria ◽  
Genes Encoding ◽  
Initial Appearance ◽  
Time Courses ◽  
Myelinating Schwann Cell ◽  
Cellular Phenotypes

The transcription factors Krox-20 and SCIP each play important roles in the differentiation of Schwann cells. However, the genes encoding these two proteins exhibit distinct time courses of expression and yield distinct cellular phenotypes upon mutation. SCIP is expressed prior to the initial appearance of Krox-20, and is transient in both the myelinating and non-myelinating Schwann cell lineages; while in contrast, Krox-20 appears approximately 24 hours after SCIP and then only within the myelinating lineage, where its expression is stably maintained into adulthood. Similarly, differentiation of SCIP−/− Schwann cells appears to transiently stall at the promyelinating stage that precedes myelination, whereas Krox-20(−/−) cells are, by morphological criteria, arrested at this stage. These observations led us to examine SCIP regulation and Schwann cell phenotype in Krox-20 mouse mutants. We find that in Krox-20(−/−) Schwann cells, SCIP expression is converted from transient to sustained. We further observe that both Schwann cell proliferation and apoptosis, which are normal features of SCIP+ cells, are also markedly increased late in postnatal development in Krox-20 mutants relative to wild type, and that the levels of cell division and apoptosis are balanced to yield a stable number of Schwann cells within peripheral nerves. These data demonstrate that the loss of Krox-20 in myelinating Schwann cells arrests differentiation at the promyelinating stage, as assessed by SCIP expression, mitotic activity and susceptibility to apoptosis.

Three markers of adult non-myelin-forming Schwann cells, 217c(Ran-1), A5E3 and GFAP: development and regulation by neuron-Schwann cell interactions

Development ◽  
1990 ◽  
Vol 109 (1) ◽  
pp. 91-103 ◽  
Author(s):  
K.R. Jessen ◽  
L. Morgan ◽  
H.J. Stewart ◽  
R. Mirsky
Keyword(s):  
Sciatic Nerve ◽  
Schwann Cell ◽  
Schwann Cells ◽  
Cell Signalling ◽  
Surface Proteins ◽  
Developmental Changes ◽  
Rat Sciatic Nerve ◽  
Ngf Receptor ◽  
Cultured Schwann Cells ◽  
Do So

Immunohistochemical methods are used to investigate in detail the development and regulation of three proteins (217c(Ran-1), A5E3 and GFAP) specifically associated with adult non-myelin-forming Schwann cells in the rat sciatic nerve, from embryo day 15 to maturity. 217c(Ran-1), which is probably the NGF-receptor, and A5E3 are expressed by the majority of cells in the nerve at embryo day 15 and by essentially all cells at embryo day 18. GFAP first appears at embryo day 18; this is an intrinsically programmed developmental event which occurs in cultured Schwann cells even in the absence of serum. Postnatally, the expression of 217c(Ran-1), A5E3 and GFAP is suppressed in cells that form myelin but retained in non-myelin-forming Schwann cells. Mature myelin-forming cells nevertheless maintain the potential to express all three proteins but will only do so if removed from contact with myelinated axons. In neuron-free cultures Schwann cells express all three proteins. This work, together with our previous observations on N-CAM, shows that removal of a diverse set of surface proteins and a change in intermediate filament expression is one of the major consequences of axon to Schwann cell signalling during myelination in the rat sciatic nerve. Unlike myelin-forming cells, adult non-myelin-forming Schwann cells remain very similar to embryonic and newborn cells with respect to expression of surface proteins, in contrast to the previously established developmental changes that occur in their surface lipids.

scholarly journals The neurotrophin receptor, gp75, forms a complex with the receptor tyrosine kinase TrkA.

1996 ◽  
Vol 132 (5) ◽  
pp. 945-953 ◽  
Author(s):  
A H Ross ◽  
M C Daou ◽  
C A McKinnon ◽  
P J Condon ◽  
M B Lachyankar ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Growth Factor Receptor ◽  
Neurotrophin Receptor ◽  
Secondary Antibody ◽  
Intact Cells ◽  
Chimeric Receptors ◽  
Ngf Receptor ◽  
Cell Expression ◽  
Insect Cell Expression ◽  
Intracellular Domains

The high-affinity NGF receptor is thought to be a complex of two receptors , gp75 and the tyrosine kinase TrkA, but direct biochemical evidence for such an association had been lacking. In this report, we demonstrate the existence of such a gp75-TrkA complex by a copatching technique. Gp75 on the surface of intact cells is patched with an anti-gp75 antibody and fluorescent secondary antibody, the cells are then fixed to prevent further antibody-induced redistributions, and the distribution of TrkA is probed with and anti-TrkA antibody and fluorescent secondary antibody. We utilize a baculovirus-insect cell expression of wild-type and mutated NGF receptors. TrkA and gp75 copatch in both the absence and presence of NGF. The association is specific, since gp75 does not copatch with other tyrosine kinase receptors, including TrkB, platelet-derived growth factor receptor-beta, and Torso (Tor). To determine which domains of TrkA are required for copatching, we used a series of TrkA-Tor chimeric receptors and show that the extracellular domain of TrkA is sufficient for copatching with gp75. A chimeric receptor with TrkA transmembrane and intracellular domains show partial copatching with gp75. Deletion of the intracellular domain of gp75 decreases but does not eliminate copatching. A point mutation which inactivates the TrkA kinase has no effect on copatching, indicating that this enzymatic activity is not required for association with gp75. Hence, although interactions between the gp75 and TrkA extracellular domains are sufficient for complex formation, interactions involving other receptor domains also play a role.

scholarly journals Neurons regulate Schwann cell genes by diffusible molecules.

1993 ◽  
Vol 123 (1) ◽  
pp. 237-243 ◽  
Author(s):  
L M Bolin ◽  
E M Shooter
Keyword(s):  
Schwann Cell ◽  
Schwann Cells ◽  
Peripheral Nerve Regeneration ◽  
Cell Types ◽  
Pou Domain ◽  
Absolute Requirement ◽  
Ngf Receptor ◽  
Neuronal Regulation ◽  
Myelin Gene

Successful peripheral nerve regeneration and functional recovery require the reestablishment of the neuron-Schwann cell relationship in the regenerating rat sciatic nerve, neurons differentially regulate Schwann cell genes. The message for the low-affinity NGF receptor, p75NGFR, is induced in Schwann cells distal to the injury and is repressed as regenerating axons make contact with these cells. The inverse is true for mRNA of the myelin gene P0; expression decreases distal to injury and increases as new axons contact Schwann cells and a program of myelination is initiated. Using an in vitro co-culture paradigm in which primary neurons and adult Schwann cells are separated by a microporous membrane, we show that axon contact is not an absolute requirement for neuronal regulation of Schwann cell genes. In this system neurons but not other cell types, repress the expression of Schwann cell p75NGFR while inducing the expression of the POU domain transcription factor, suppressed cAMP inducible POU, and myelin P0. These results demonstrate that regenerating axons can direct the Schwann cell genetic program from a distance through diffusible molecules.

The Zinc Finger Transcription Factor Zif268/Egr-1 Is Essential for Schwann Cell Expression of the p75 NGF Receptor

1995 ◽  
Vol 6 (4) ◽  
pp. 337-348 ◽  
Author(s):  
Savita S. Nikam ◽  
Gihan I. Tennekoon ◽  
Barbara A. Christy ◽  
Jun E. Yoshino ◽  
J.Lynn Rutkowski
Keyword(s):  
Transcription Factor ◽  
Schwann Cell ◽  
Zinc Finger ◽  
Zinc Finger Transcription Factor ◽  
Ngf Receptor ◽  
Cell Expression
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