Studies on the control of myelinogenesis. IV. Neuronal induction of Schwann cell myelin-specific protein synthesis during nerve fiber regeneration

Politis, Michael J.; Sternberger, Nancy H.; Ederle, K; Spencer, P.S.

doi:10.1523/jneurosci.02-09-01252.1982

Cited by 81 publications

(36 citation statements)

References 17 publications

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“…NaDodSO4-PGE: 10-20% T (total gel concentration), 1% C (gel crosslinking); 10 (Fig. 1D) by its shift in molecular weight from 29,000 in the presence of 5% 2-mercaptoethanol to 26,200 in the absence of this reducing agent (24). This shift in molecular weight is in agreement with similar observations made by Cammer et al (28) and is used for the positive identification of this glycoprotein in the transected nerve.…”

Section: Resultssupporting

confidence: 88%

Schwann cell expression of a major myelin glycoprotein in the absence of myelin assembly.

Poduslo¹,

Berg²,

Dyck³

1984

Proc. Natl. Acad. Sci. U.S.A.

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Quiescent Schwann cells in the distal segment of the permanently transected nerve produced basal levels of the major myelin glycoprotein, P0, in the absence of myelin assembly. Low levels of Po could be detected at 35 days after transection by autoradiographic analysis of radioiodinated lectin binding after protein separation by high-resolution sodium dodecyl sulfate pore gradient electrophoresis and by fluorographic analysis after electrophoresis of [3H] MATERIALS AND METHODSSciatic nerves from Sprague-Dawley rats (200 g), anesthetized with intraperitoneal sodium pentobarbital, were exposed below the sciatic notch, ligated twice with 4/0 sterile sutures, and transected between the pairs of sutures (11). Each end of the transected nerve was undercut for a distance of 10 mm, repositioned by 180°, and sutured to adjacent muscle. This procedure is designed to inhibit the outgrowth of regenerating axons from the proximal segment and prevent their subsequent entry into the distal segment. After closure of the wound, the animals were maintained in separate cages on shavings for 35 days. At this time, the animals were anesthetized, and the entire lengths of the distal segments of the sciatic, tibial, peroneal, and sural nerves were removed and processed. Morphometric evaluation at the light and electron microscopic level showed no new myelinated fibers at 35 days after transection, although new myelinated fibers (<1.5%, expressed as myelin percent of total area of transverse section of endoneurium) were observed at later times (70 and 105 days), indicating reinnervation (unpublished data). Biochemical studies were performed on the endoneurium, which was removed from the perineurium and epineurium by microdissection (18) and homogenized in deionized distilled water with a ground-glass homogenizer. A uniform suspension was obtained which was then treated with 10% NaDodSO4, sonicated for 1 hr, and centrifuged in the 300 A-100 rotor of the Beckman Airfuge at 197,000 x g at 40C. Aliquots of the NaDodSO4-solubilized supernatant were taken for protein determination (19), and the proteins were separated by NaDodSO4 pore gradient electrophoresis (Na- (20,21). Proteins were detected by Coomassie blue stain, and glycoproteins were evaluated by using radioiodinated lectins applied directly to the slab gel after electrophoresis (22,23). In several experiments, radioactive precursor incorporation studies were performed directly on endoneurial slices at 35 days after transection in modified Krebs mammalian Ringer solution (24). RESULTSAt 35 days after permanent transection, analysis of the detergent-solubilized endoneurium by NaDodSO4-PGE suggests that P0 cannot be detected by Coomassie blue stain (sensitivity -100 ng) (Fig. 1A). In contrast, Po is the major endoneurial protein of the normal sciatic nerve (control). This lack of Abbreviation: PGE, pore gradient electrophoresis. 1864The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement...

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Section: Resultssupporting

confidence: 88%

Schwann cell expression of a major myelin glycoprotein in the absence of myelin assembly.

Poduslo¹,

Berg²,

Dyck³

1984

Proc. Natl. Acad. Sci. U.S.A.

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“…Schwann cell production of myelin components is substantially downregulated following nerve transection or dissociation from the axon under tissue culture conditions (Mirsky et al, 1980;Spencer et al, 198 1;Politis et al, 1982;Winter et al, 1982;Poduslo et al, 1984Poduslo et al, , 1985Eccleston et al, 1987;Trapp et al, 1988;LeBlanc and Poduslo, 1990;Rutkowski et al, 1990;Yao et al, 1990). These data have been interpreted generally to indicate a continuing requirement for the axon in myelin maintenance.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, axonal contact appears to be the primary determinant in induction of the myelinating Schwann cell phenotype Spencer, 1975, 1976;Aguayo et al, 1976) which is characterized by synthesis of myelin components such as P,, P,, MBP, and galactocerebroside (Mirsky et al, 1980;Politis et al, 1982;Winter et al, 1982;Eccleston et al, 1987;Ranscht et al, 1987) and their assembly into myelin membranes. Conversely, loss of the axon from myelinated fibers following surgical or neurotoxic lesions results in rapid myelin lysis (Asbury, 1975;Allt, 1976).…”

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confidence: 99%

“…Conversely, loss of the axon from myelinated fibers following surgical or neurotoxic lesions results in rapid myelin lysis (Asbury, 1975;Allt, 1976). The Schwann cell resumes a less differentiated, nonmyelinated phenotype in which the synthesis of myelin and basal lamina components (Mirsky et al, 1980;Spencer et al, 198 1;Politis et al, 1982;Winter et al, 1982;Poduslo et al, 1984Poduslo et al, , 1985R. P. Bunge et al, 1986;Trapp et al, 1988;M.…”

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Myelin sheath survival following axonal degeneration in doubly myelinated nerve fibers

Kidd

1991

J. Neurosci.

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Axonal contact plays a critical role in initiating myelin formation by Schwann cells. However, recent studies of “double myelination” have indicated that myelin maintenance continues in Schwann cells completely displaced from physical contact with the axon. This raises the possibility either that diffusible trophic factors are produced by the axon, or that the axon is not required for myelin maintenance by these displaced Schwann cells. To test these hypotheses, the axons involved in double myelination in the mouse superior cervical ganglion (SCG) were transected surgically by a transganglionic lesion. The inferior pole of the SCG was resected to limit axonal regeneration. This method produced a typical Wallerian pattern of degeneration in the superior pole, without compromising the blood supply or introducing nonspecific trauma. EM analysis at 1 and 5 d postoperatively showed that initially the axon degenerated, followed by breakdown of the inner myelin sheath. In those configurations where the outer Schwann cell was only partly displaced from the axon, the outer myelin sheath degenerated simultaneously. However, in completely displaced internodes the outer sheath survived degeneration of the axon and inner sheath. Outer internodes remained intact for at least 5 weeks after transection (the longest time point in this study), at which time they enclosed reorganized processes of the inner Schwann cells, their basal lamina, and numerous collagen fibrils. Axonal regeneration within surviving outer internodes was rare and was characterized by the development of typical Remak ensheathment by the inner Schwann cells. We conclude that in the mouse SCG, myelin maintenance does not depend on the continued presence of the axon. These data suggest further that myelin breakdown in Wallerian degeneration may be initiated by mechanisms other than absence of a viable axon.

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“…In contrast to these proteins, however, P 0 is not expressed by oligodendrocytes in the central nervous system. The pronounced up-regulation of P 0 biosynthesis observed at the onset of overt myelination appears to be triggered by a signal associated with the surface of axons (15,16). This signal may be transduced intracellularly through elevation of cyclic AMP: in cultured Schwann cells, cAMP-elevating agents such as forskolin potentiate P 0 gene expression and strongly potentiate expression of less abundantly expressed myelin-specific genes (16,17).…”

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Multiple Regulatory Elements Control Transcription of the Peripheral Myelin Protein Zero Gene

Brown

Lemke

1997

Journal of Biological Chemistry

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The gene encoding protein zero (P 0 ), the most abundant protein of peripheral nervous system myelin, is expressed uniquely in Schwann cells. Previous studies have demonstrated that much of the cell type specificity of this expression is due to transcriptional control elements in the 1.1-kilobase pair 5-regulatory region of the gene. We have now analyzed this region and have identified a set of functional elements in the 500 base pairs proximal to the transcription start site. DNA sequence conservation within the 5 regions of the human, mouse, and rat P 0 genes correlates closely with the results of promoter deletion analysis of the 1.1-kilobase pair region assayed in Schwann cell cultures and reveals a potent proximal region from position ؊350 to ؉45. Sites of protein/DNA interaction within the proximal 500 base pairs of the promoter were identified by footprinting assays. Functional transcriptional elements were identified within the protected regions in the proximal promoter by mutation and transient transfection analysis in P 0 -expressing cell lines. The core (or basal) P 0 promoter is identified as two regulatory elements, a G/Crich element that binds nuclear factor Sp1 and a CAAT box that binds NF-Y. These core elements are essential for the transcription observed from the transfected promoter in cultured Schwann cells.The myelin sheath is a specialized membranous organelle of the vertebrate nervous system. Elaborated by oligodendrocytes in the central nervous system and by Schwann cells in the peripheral nervous system (PNS), 1 this organelle consists of a large sheet of plasma membrane that is repeatedly wrapped and very tightly compacted around axons (1). Myelin is essential for the rapid conduction of action potentials in vertebrates, and human diseases that compromise the integrity of the sheath (e.g. peripheral neuropathies in the PNS and multiple sclerosis in the central nervous system) are generally debilitating (2). The elaboration of myelin requires a substantial biosynthetic up-regulation of plasma membrane lipids and proteins, several of which are unique to the myelin sheath (3). In the PNS, the most abundant of these is protein zero (P 0 ), a 31-kilodalton, immunoglobulin-related, transmembrane glycoprotein that accounts for greater than 50% of the protein in mammalian PNS myelin (4). The mRNA encoding this protein is estimated to account for nearly 8% of the poly(A) RNA in actively myelinating Schwann cells (5).A variety of studies have demonstrated that P 0 is essential for peripheral nerve development and function. Mice in which the P 0 gene has been deleted exhibit a severe peripheral neuropathy that includes hypomyelination, loss of motor control, tremors, and grossly abnormal myelin sheaths (6, 7). Furthermore, mutations in the P 0 gene account for a variety of inherited human peripheral neuropathies, including Charcot-MarieTooth disease type 1B, Dejerine-Sottas syndrome, and congenital hypomyelination (8 -12).High level P 0 expression is a distinctive feature of terminal differentiatio...

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Studies on the control of myelinogenesis. IV. Neuronal induction of Schwann cell myelin-specific protein synthesis during nerve fiber regeneration

Cited by 81 publications

References 17 publications

Schwann cell expression of a major myelin glycoprotein in the absence of myelin assembly.

Schwann cell expression of a major myelin glycoprotein in the absence of myelin assembly.

Myelin sheath survival following axonal degeneration in doubly myelinated nerve fibers

Multiple Regulatory Elements Control Transcription of the Peripheral Myelin Protein Zero Gene

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