What is the difference between myelin sheath and schwann cell

This YAP could then be dephosphorylated and become activated to increase myelin production and longitudinal deposition Figure 4. Schematics illustrating the model of mechano-sensitivity in mSC during postnatal body growth. A In the absence of axonal elongation, in adult nerves, the relaxed actin cytoskeleton anchored to the axon via axo-glial junctions and to the basal lamina via Dystroglycan-Utrophin-Periaxin complexes sequesters YAP. Inactive YAP does not reach the nucleus and myelin production and deposition is halted.

B During postnatal body growth or after artificial nerve elongation, axons extend and this stretches the actin cytoskeleton which is also bound to the static basal lamina. YAP is then released from its cytoskeleton prison and can be activated.

It enters the nucleus and stimulates myelin production and deposition in order to elongate myelin sheaths. An intriguing question to be raised is whether mSC can grow over each other, crossing the boundaries indicated by the nodes of Ranvier. In the very large majority of nerves, such overlapping never occurs, suggesting a molecular mechanism exists that prevents myelin sheath invasion.

Nevertheless this has actually been reported in the sympathetic nervous system of adult mice and rats superior cervical ganglion in particular Kidd and Heath, and in the spinal roots of new born cats Berthold and Remahl, The investigators indicate that this overlapping myelin sheath is quite common at this age and internodal length is very variable.

Myelinating cells compete for a piece of axon to myelinate and the losing one can demyelinate and move to another axon and make a second attempt at myelination in a new location Berthold and Remahl, This dynamic process ceases a few weeks later as myelin sheath starts to elongate along the axons, resulting in an internodal length that is comparable to other nerves in the adult animal. Taken together this indicates that mSC boundaries exist and are actively maintained during myelination.

In some in vivo experiments, mSC of the mouse sciatic nerve were infected with viruses expressing Crb3 silencing shRNA together with a fluorescent probe. This leads to sparsely Crb3-silenced fluorescent mSC that over-elongated on their axons, surrounded by non-silenced cells Fernando et al. However, these over-elongating myelinating cells never crossed their boundaries with the next cells: nodes were always localized between the myelin segment and overlapping myelin sheaths were never observed, even when examined by electron microscopy.

This indicates that despite the loss of Crb3 in microvilli and the disruption of the regulation of longitudinal myelin sheath growth, the boundaries remain intact. Myelinating cells surrounding the over-elongating cell keep their distances, buffer the overgrowth and finally do not change much their size.

This suggests that homogenous myelin sheath internodal length on the same axon is more likely due to a homogenous longitudinal myelination pace instead of cell—cell competition.

One of the most common pathologies affecting peripheral myelination is traumatic nerve injury. Injury induces SC demyelination, which is followed by a remyelination process when the axon has grown back. It has been long known that when SC remyelinate, while they reach their optimal thickness, they never reach their previous internodal length and remain shorter Jacobs and Cavanagh, ; Hildebrand et al. The reason for this failure is not known but recent data show that, before to remyelinate, repaired Schwann cells are longer than their final size Gomez-Sanchez et al.

This suggests that extrinsic cues are responsible for the final size of remyelinated cells. The mechano-sensitivity of mSC to peripheral nerve stretching during postnatal body growth can suggest a mechanism: the myelin sheath elongation process requiring YAP and controlled by Crb3-HIPPO is only active when YAP is activated by nerve stretching. In the absence of this stretching, such as during static co-culture myelination, myelin sheath remains appropriately short and close to its starting size.

When cells start to remyelinate after a pathologic demyelination occurring in adults there is also no body growth to stretch the nerves and to reengage the earlier YAP driven process, so the myelin sheath internodes do not fully elongate and remain short.

In most cases, sections of locally shortened myelin segments are not sufficient to globally impair nerve conduction velocity, so no therapy is needed. However, if remyelination is more generalized, then permanent detrimental outcomes may occur.

However, despite this remyelination permanent sequels are generally observed Willison et al. In this case, a drug or a compound that lift the inhibition of Crb3 on YAP activity may help to restore longer myelin sheath during remyelination. Some genetic diseases also lead to a reduced internodal length outcome: Periaxin and Laminin 2 also called Merosin mutations induce short myelin sheath internodes in peripheral nerves and lead to CMT4F and Lama2 neuromuscular disease respectively Gillespie et al.

In both cases the molecular complex that links basal lamina to the mSC cytoskeleton is affected, suggesting this complex is required for internodal elongation during body growth. Recent experiments in mice have confirmed this hypothesis. Mutant Lama2 mouse line mimics the short internodal lengths found in human patients and show an impaired peripheral nerve conduction Patton et al.

Myelinating cells of these mice have a reduced amount of active YAP in their nuclei with no change in Crb3 expression or in the amount of phosphorylated inactive YAP Fernando et al. This suggests that the deficiency in active YAP does not result from more inactivation by the Crb3-HIPPO pathway but more likely from the lack of activation through the mechano-sensitive mechanism during nerve stretching.

This is consistent with the model presented previously where the basal lamina, and the complex that links basal lamina to the actin cytoskeleton, is important for the cell to detect the axonal extension during peripheral nerve stretching Figure 4. SCs lacking such a functional complex may be insensitive to the axonal extension and therefore do not extend their myelin sheath correctly.

In any case the deficiency in active YAP is indeed one of the causes of the disease; when YAP is activated through the silencing of Crb3 in mutant Lama2 cells the correct internodal is partially restored compared to controls Fernando et al. Taken together the data presented in this review elaborates on how Schwann cell myelination is controlled, not only through cell polarity factors, but also via cytoskeleton, mechanosensor, junctional proteins, signaling pathways, and co-transcription factors.

These pathways act in concert to translate postnatal body growth into an adjusted and optimized myelin sheath internodal length. Of course, many points remain hypothetical and their further study is required in order to provide a clear picture of the myelin sheath formation and the pathological causes of peripheral nerve diseases with short internodes.

In addition, as oligodendrocyte myelin sheath internodal length is also critical for the function of the central nervous system Hamilton et al. The author confirms being the sole contributor of this work and approved it for publication. The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Molecular mechanisms of node of Ranvier formation. Current Opinion in Cell Biology 20 , — Cell Signaling. Ion Channel. Cell Adhesion and Cell Communication. Aging and Cell Division. Endosomes in Plants. Ephs, Ephrins, and Bidirectional Signaling. Ion Channels and Excitable Cells. Signal Transduction by Adhesion Receptors. Citation: Susuki, K. Nature Education 3 9 How does our nervous system operate so quickly and efficiently? The answer lies in a membranous structure called myelin.

Aa Aa Aa. Information Transmission in the Body. Figure 1. Figure Detail. Axonal Signaling Regulates Myelination. Figure 2: The fate of demyelinated axons. The case in the CNS is illustrated.

Research in Myelin Biology and Pathology. Figure 3. References and Recommended Reading Brinkmann, B. Waxman, S. The Axon: Structure, Function and Pathophysiology.

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Saltwater Science. Now while the structure and the function of the little myelin segments is the same, a big difference between the Schwann cells in the peripheral nervous system and the oligodendrocytes in the central nervous system is that a Schwann cell only produces the myelin sheath for one segment of only one axon.

It's not myelinating multiple neurons, like oligodendrocytes do. Now, let's take a little closer look at one of these areas of myelin sheath. And let's cut through this segment of myelin, just like this. And we'll look at it this way, like we're looking down from the end of the axon. And this is going to look just like the myelin sheath for a central axon. Here's the axon. And we're looking at it end-on. And the cell membrane of the Schwann cell, which is this material we call myelin, that's very rich in lipid, is just going to be wrapped again and again and again, very thinly and very tightly, like a role of tape, around the axon.

Now for a Schwann cell, this is almost the entirety of its cell membrane. And then it's just going to have this little lump on the outside that's going to be sort of like a soma because it's going to have a nucleus and it's going to have most of the cytoplasm of a Schwann cell. But most of its membrane is actually wrapped around the axon as the myelin sheath.

In addition to these functions, Schwann cells also appear to influence neurons, and vice versa, through exchange of a variety of substances.