Editing Schwann cell

{{Short description|Glial cell type}}
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| caption         = Schwann&nbsp;cells (red, cylindral cells at bottom) on a neuron (yellow) in the PNS
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'''Schwann cells''' or '''neurolemmocytes''' (named after German physiologist [[Theodor Schwann]]) are the principal [[glia]] of the [[peripheral nervous system]] (PNS). Glial cells function to support [[neurons]] and in the PNS, also include [[Satellite glial cell|satellite cells]], [[olfactory ensheathing cells]], enteric glia and glia that reside at sensory nerve endings, such as the [[Pacinian corpuscle]]. The two types of Schwann cells are [[Myelin|myelinating]] and [[Nonmyelinating Schwann cell|nonmyelinating]].<ref name="Bhatheja">{{cite journal |last1=Bhatheja |first1=K |last2=Field |first2=J |title=Schwann cells: origins and role in axonal maintenance and regeneration |journal=The International Journal of Biochemistry & Cell Biology |date=2006 |volume=38 |issue=12 |pages=1995–99 |doi=10.1016/j.biocel.2006.05.007 |pmid=16807057}}</ref>  Myelinating Schwann cells wrap around axons of motor and sensory neurons to form the [[myelin sheath]].
The Schwann cell promoter is present in the [[Upstream and downstream (DNA)|downstream]] region of the human [[dystrophin]] gene that gives shortened [[Transcription (biology)|transcript]] that are again synthesized in a tissue-specific manner.

During the development of the PNS, the regulatory mechanisms of myelination are controlled by feedforward interaction of specific genes, influencing transcriptional cascades and shaping the morphology of the myelinated nerve fibers.<ref name=":3" />

Schwann cells are involved in many important aspects of peripheral [[nerve]] biology{{snd}}the conduction of [[action potential|nervous impulses]] along [[axon]]s, nerve development and [[nerve regeneration|regeneration]], trophic support for [[neuron]]s, production of the nerve extracellular matrix, modulation of neuromuscular [[Synaptic vesicle|synaptic]] activity, and presentation of [[antigen]]s to [[T-lymphocytes]].

[[Charcot–Marie–Tooth disease]], [[Guillain–Barré syndrome]] (acute inflammatory demyelinating polyradiculopathy type), [[schwannomatosis]], [[chronic inflammatory demyelinating polyneuropathy]], and [[Mycobacterium leprae|leprosy]] are all [[peripheral neuropathy|neuropathies]] involving Schwann cells.

==Structure==
{{Neuron map|Schwann cells wrapped around an axon}}
Schwann cells are a variety of [[glial cell]]s that keep peripheral nerve fibres (both myelinated and unmyelinated) alive. In myelinated axons, Schwann cells form the [[myelin]] sheath. The sheath is not continuous. Individual myelinating Schwann cells cover about 1&nbsp;mm of an axon<ref>{{cite book |last1=Tortora |first1=Gerard J. |title=Principles of Anatomy and Physiology |date=2017 |publisher=Wiley |location=US |isbn=978-1-119-32064-7 |page=412 |edition=15th}}</ref>{{snd}}equating to about 1000 Schwann cells along a 1-m length of the axon. The gaps between adjacent Schwann cells are called [[nodes of Ranvier]].

[[ST8SIA1|9-O-Acetyl GD3]] [[ganglioside]] is an acetylated glycolipid which is found in the cell membranes of many types of vertebrate cells. During peripheral [[nerve regeneration]], 9-O-acetyl GD3 is expressed by Schwann cells.<ref>{{cite journal |last1=Túlio Ribeiro-Resende |first1=Victor |last2=Lopes |first2=Michelle |date=2010 |title=Involvement of 9-O-Acetyl GD3 Ganglioside in Mycobacterium leprae Infection of Schwann Cells |journal=J. Biol. Chem.|volume= 285|issue=44 |pages=34086–96 |doi=10.1074/jbc.M110.147272 |pmid=20739294 |pmc=2962507|doi-access=free }}</ref>

==Function==
The [[vertebrate]] [[nervous system]] relies on the myelin sheath for [[Insulator (electrical)|insulation]] and as a method of decreasing membrane [[capacitance]] in the axon. The [[action potential]] jumps from node to node, in a process called [[saltatory conduction]], which can increase [[Electrical conduction|conduction]] velocity up to 10 times, without an increase in axonal diameter. In this sense, Schwann cells are the PNS's analogues of the [[central nervous system]]'s [[oligodendrocyte]]s. However, unlike oligodendrocytes, each myelinating Schwann cell provides insulation to only one axon (see image). This arrangement permits saltatory conduction of action potentials with [[wiktionary:propagation|repropagation]] at the nodes of Ranvier. In this way, myelination greatly increases speed of conduction and saves energy.<ref>Kalat, James W. ''Biological Psychology'', 9th ed. US: Thompson Learning, 2007.{{Page needed|date=April 2011}}</ref>

Nonmyelinating Schwann cells are involved in maintenance of axons and are crucial for neuronal survival. Some group around smaller axons ([http://www.liv.ac.uk/~rbj/RBJ/rbjteaching/Schwann%20Cells.htm External image here]) and form [[C fiber#Remak bundles|Remak bundles]].

Myelinating Schwann cells begin to form the myelin sheath in mammals during fetal development and work by spiraling around the axon, sometimes with as many as 100 revolutions.  A well-developed Schwann cell is shaped like a rolled-up sheet of paper, with layers of myelin between each coil. The inner layers of the wrapping, which are predominantly [[cell membrane|membrane]] material, form the myelin sheath, while the outermost layer of nucleated [[cytoplasm]] forms the [[neurilemma]]. Only a small volume of residual cytoplasm allows communication between the inner and outer layers. This is seen [[Histology|histologically]] as the [[Schmidt-Lantermann incisure]].

=== Regeneration ===
Schwann cells are known for their roles in supporting [[nerve regeneration]].<ref>{{cite journal |pages=1995–99 |doi=10.1016/j.biocel.2006.05.007 |title=Schwann cells: Origins and role in axonal maintenance and regeneration |year=2006 |last1=Bhatheja |first1=Kanav |last2=Field |first2=Jeffrey |journal=The International Journal of Biochemistry & Cell Biology |volume=38 |issue=12 |pmid=16807057}}</ref> Nerves in the PNS consist of many axons myelinated by Schwann cells. If damage occurs to a nerve, the Schwann cells aid in digestion of its axons ([[phagocytosis]]). Following this process, the Schwann cells can guide regeneration by forming a type of tunnel that leads toward the target neurons. This tunnel is known as [[band of Büngner]], a guidance track for the regenerating axons, which behaves like an endoneural tube. The stump of the damaged axon is able to sprout, and those sprouts that grow through the Schwann-cell "tunnel" do so at the rate around 1&nbsp;mm/day in good conditions. The rate of regeneration decreases with time. Successful axons can, therefore, reconnect with the muscles or organs they previously controlled with the help of Schwann cells, but specificity is not maintained and errors are frequent, especially when long distances are involved.<ref>Carlson, Neil R. ''Physiology of Behavior'', 9th ed. US: Pearson Education, Inc., 2007.{{Page needed|date=April 2011}}</ref> Because of their ability to impact regeneration of axons, Schwann cells have been connected to [[preferential motor reinnervation]], as well. 
If Schwann cells are prevented from associating with axons, the axons die. Regenerating axons will not reach any target unless Schwann cells are there to support them and [[Axon guidance|guide]] them. They have been shown to be in advance of the [[growth cone]]s.  
Schwann cells are essential for the maintenance of healthy axons. They produce a variety of factors, including [[neurotrophin]]s, and also transfer essential molecules across to axons.[[Image:Cultured schwann cell.jpg|thumb|left|alt=Schwann cell.|A Schwann cell in culture]]

== Genetics ==
=== Schwann cell formation ===

==== Sox10 ====
SOX10 is a transcription factor active during embryonic development and abundant evidence indicates that it is essential for the generation of glial lineages from trunk crest cells.<ref name=":0">{{cite journal|last1=Britisch, S.|title=The transcription factor Sox10 is a key regulator of peripheral glial development|journal=Genes Dev.|volume=15|issue=1|pages=66–78|display-authors=etal|doi=10.1101/gad.186601|pmid=11156606|year=2001|pmc=312607}}</ref><ref name=":1">{{cite journal|last1=Paratore, C., Goerich, D. E., Suter, U., Wegner, M. & Sommer, L.|title=Survival and glial fate acquisition of neural crest cells are regulated by an interplay between the transcription factor Sox10 and extrinsic combinatorial signalling|journal=Development|year=2001 |volume=128|issue=20 |pages=3949–61|doi=10.1242/dev.128.20.3949 |pmid=11641219}}</ref> When SOX10 is inactivated in mice, satellite glia and Schwann cell precursors fail to develop, though neurons are generated normally without issue.<ref name=":0" /> In the absence of SOX10, neural crest cells survive and are free to generate neurons, but glial specification is blocked.<ref name=":1" /> SOX10 might influence early glial precursors to respond to neuregulin 1<ref name=":0" /> (see below).

==== Neuregulin 1 ====
Neuregulin 1 (NRG1) acts in a number of ways to both promote the formation and ensure the survival of immature Schwann cells.<ref>{{Cite journal|last=Shah, N. M.|date=1994|title=Glial growth factor restricts mammalian neural crest stem cells to glial fate|journal=Cell|volume=77|issue=3|pages=349–60|doi=10.1016/0092-8674(94)90150-3|pmid=7910115|s2cid=20297598|display-authors=etal}}</ref> During embryonic development, NRG1 inhibits the formation of neurons from neural crest cells, instead contributing to neural crest cells being led down a path to gliogenesis. NRG1 signaling is not, however, required for glial differentiation from the neural crest.<ref name=":2">{{Cite journal|author1=Jessen, K. R.  |author2=Misky, R. |name-list-style=amp |date=2005|title=The origin and development of glial cells in peripheral nerves|journal=Nature Reviews Neuroscience|volume=6|issue=9 |pages=671–82|doi=10.1038/nrn1746|pmid=16136171|s2cid=7540462 }}</ref>

NRG1 plays important roles in the development of neural crest derivatives. It is required for neural crest cells to migrate past the site of dorsal root ganglia to find the ventral regions of sympathetic gangliogenesis.<ref>{{Cite journal|last=Britisch, S.|date=1998|title=The ErbB2 and ErbB3 receptors and their ligand, neuregulin-1 are essential for development of the sympathetic nervous system|journal=Genes Dev.|volume=12|issue=12|pages=1825–36|doi= 10.1101/gad.12.12.1825|pmid=9637684|display-authors=etal|pmc=316903}}</ref> It is also an essential axon-derived survival factor and a mitogen for Schwann cell precursors.<ref>{{Cite journal|last=Dong, Z.|date=1995|title=NDF is a neuron-glia signal and regulates survival, proliferation, and maturation of rat Schwann cell precursors|journal=Neuron|volume=15|issue=3|pages=585–96|doi=10.1016/0896-6273(95)90147-7|pmid=7546738|s2cid=15332720|display-authors=etal|doi-access=free}}</ref> It is found in the dorsal root ganglion and motor neurons at the point in time that Schwann cell precursors begin to populate spinal nerves and therefore influences Schwann cell survival.<ref name=":2" /> In embryonic nerves, the transmembrane III isoform likely is the primary variant of NRG1 responsible for survival signals. In mice that lack the transmembrane III isoform, Schwann cell precursors are eventually eliminated from spinal nerves.<ref>{{Cite journal|last=Wolpowitz, D.|date=2000|title=Cysteine-rich domain isoforms of the neuregulin-1 gene are required for maintenance of peripheral synapses|journal=Neuron|volume=25|issue=1|pages=79–91|doi=10.1016/s0896-6273(00)80873-9|pmid=10707974|s2cid=16187922|display-authors=etal|doi-access=free}}</ref>

=== Formation of myelin sheath ===

==== P0 ====
[[Myelin protein zero]] (P0) is a cell-adhesion molecule belonging to the immunoglobulin superfamily and is the major component of peripheral myelin, constituting over 50% of the total protein in the sheath.<ref>{{Cite journal|last1=Greenfield|first1=S.|last2=Brostoff|first2=S.|last3=Eylar|first3=E. H.|last4=Morell|first4=P.|date=1973|title=Protein composition of myelin of the peripheral nervous system|pmid=4697881|journal=Journal of Neurochemistry|volume=20|issue=4|pages=1207–16|doi=10.1111/j.1471-4159.1973.tb00089.x|s2cid=30385476}}</ref><ref>{{Cite journal|last=Lemke|first=G.|date=1988|title=Unwrapping the genes of myelin|journal=Neuron|volume=1|issue=7|pages=535–43|doi=10.1016/0896-6273(88)90103-1|pmid=2483101|s2cid=27086229}}</ref> P0 has been shown to be essential for the formation of compact myelin, as P0 null mutant (P0-) mice showed severely aberrant peripheral myelination.<ref>{{Cite journal|last1=Geise|first1=K.|last2=Martini|first2=R.|last3=Lemke|first3=G|last4=Soriano|first4=P.|last5=Schachner|first5=M.|date=1992|title=Mouse P0 Gene Disruption Leads to Hypomyelination, Abnormal Expression of Recognition Molecules, and Degeneration of Myelin and Axons|journal=Cell|volume=71|issue=4|pages=565–76|doi=10.1016/0092-8674(92)90591-y |pmid=1384988|s2cid=41878912}}</ref>  Although myelination of large caliber axons was initiated in P0- mice, the resulting myelin layers were very thin and poorly compacted.  Unexpectedly, P0- mice also showed degeneration of both axons and their surround myelin sheaths, suggesting that P0 plays a role in maintaining the structural integrity of both myelin formation and the axon with which it is associated.  P0- mice developed behavioral deficits around 2 weeks of age when mice began to show signs of slight trembling.  Gross incoordination also arose as the animals developed, while trembling became more severe and some older mice developed convulsing behaviors.  Despite the array of impaired motor behavior, no paralysis was observed in these animals.  P0 is also an important gene expressed early within the Schwann cell lineage, expressed in Schwann cell precursors after differentiating from migrating [[Neural crest|neural crest cells]] within the developing embryo.<ref>{{Cite journal|last1=Jessen|first1=K.|last2=Mirsky|first2=R.|date=2005|title=The origin and development of glial cells in peripheral nerves|journal=Nature Reviews Neuroscience|volume=6|issue=9|pages=671–82|doi=10.1038/nrn1746|pmid=16136171|s2cid=7540462}}</ref>

==== Krox-20 ====

Several important transcription factors are also expressed and involved at various stages in development changing the features on the Schwann cells from an immature to mature state. One indispensable transcription factor expressed during the myelination process is Krox-20. It is a general zinc-finger transcription factor and is expressed in the rhombomeres 3 and 5.

Krox-20 is considered one of the master regulators of PNS myelination and is important in driving transcription of specific structural proteins in the myelin. It has been shown to control a set of genes responsible for interfering with this feature in the axon changing it from a pro-myelinating to myelinating state.<ref name=":4">{{Cite journal|last=Salzer|first=James|date=2015|title=Schwann cell myelination|journal= Cold Spring Harbor Perspectives in Biology|volume=7|issue=8|pages=a020529|doi=10.1101/cshperspect.a020529|pmid=26054742|pmc=4526746}}</ref> In this way, in Krox-20 double knock out mice, it has been recorded that hindbrain segmentation is affected as well as myelination of Schwann cell associated axons. Indeed, in these mice, the Schwann cells are not able to perform their myelination properly as they only wrap their cytoplasmic processes one and half turn around the axon and despite the fact that they still express the early myelin marker, late myelin gene products are absent. In addition, recent studies have also proven the importance of this transcription factor in maintaining the myelination phenotype (and requires the co-expression of Sox 10) as its inactivation leads to dedifferentiation of the Schwann cells.<ref name=":3">{{Cite journal|last1=Topilko|first1=Piotr|last2=Schneider-Maunoury|first2=Sylvie|last3=Levi|first3=Giovanni|last4=Baron-Van Evercooren|first4=Anne|last5=Chennoufi|first5=Amina Ben Younes|last6=Seitanidou|first6=Tania|last7=Babinet|first7=Charles|last8=Charnay|first8=Patrick|date=1994-10-27|title=Krox-20 controls myelination in the peripheral nervous system|journal=Nature|language=en|volume=371|issue=6500|pages=796–99|doi=10.1038/371796a0|pmid=7935840|bibcode=1994Natur.371..796T|s2cid=4333028}}</ref>

==Clinical significance==
[[Charcot–Marie–Tooth disease]] (CMT), [[Guillain–Barré syndrome]] (GBS, acute inflammatory demyelinating polyradiculopathy type), [[schwannomatosis]], and [[chronic inflammatory demyelinating polyneuropathy]] (CIDP), [[Mycobacterium leprae|leprosy]], and [[Zika Virus]] are all [[peripheral neuropathy|neuropathies]] involving Schwann cells.<ref>{{Cite journal|last1=Dhiman|first1=Gaurav|last2=Abraham|first2=R.|last3=Griffin|first3=D. |date=2019|title=Human Schwann cells are susceptible to infection with Zika and yellow fever viruses, but not dengue virus|pmid=31289325 |pmc=6616448|journal=Scientific Reports|volume=9|issue=1|pages=9951|doi=10.1038/s41598-019-46389-0|bibcode=2019NatSR...9.9951D}}</ref> 

===Transplantation===
A number of experimental studies since 2001 have implanted Schwann cells in an attempt to induce [[remyelination]] in [[multiple sclerosis]]-afflicted patients.<ref>{{cite news|url=http://www.findarticles.com/p/articles/mi_m0850/is_4_19/ai_79957646 |archive-url=https://web.archive.org/web/20070311012601/http://www.findarticles.com/p/articles/mi_m0850/is_4_19/ai_79957646 |url-status=dead |archive-date=2007-03-11 |work=Inside MS |title=First surgical transplant attempted to repair myelin |year=2001 }}</ref> In the past two decades, many studies have demonstrated positive results and potential for Schwann cell transplantation as a therapy for spinal cord injury, both in aiding regrowth and myelination of damaged CNS axons.<ref>{{cite journal |pages=453–67 |doi=10.1089/neu.2006.23.453 |title=Schwann Cell Transplantation for Repair of the Adult Spinal Cord |year=2006 |last1=Oudega |first1=Martin |last2=Xu |first2=Xiao-Ming |journal=Journal of Neurotrauma |volume=23 |issue=3–4 |pmid=16629629}}</ref>  Schwann cell transplants in combination with other therapies such as Chondroitinase ABC have also been shown to be effective in functional recovery from spinal cord injury.<ref>{{cite journal|last=Fouad|first=Karim|author2=Lisa Schnell |author3=Mary B. Bunge |author4=Martin E. Schwab |author5=Thomas Liebscher |author6=Damien D. Pearse |title=Combining Schwann Cell Bridges and Olfactory-Ensheathing Glia Grafts with Chondroitinase Promotes Locomotor Recovery after Complete Transection of the Spinal Cord|journal=The Journal of Neuroscience|volume=25|issue=5|pages=1169–78|date=2 February 2005|doi=10.1523/JNEUROSCI.3562-04.2005|pmid=15689553|pmc=6725952|doi-access=free}}</ref>

== See also ==
* [[Electrophysiology]]
* [[Hodgkin–Huxley model]]
* [[Mesaxon]]
* [[Neurotransmission]]
* [[Olfactory ensheathing cell]]
* [[Perisynaptic schwann cells]]
* [[Schwannoma]]
* [[List of human cell types derived from the germ layers]]
* [[List of distinct cell types in the adult human body]]

== References ==
{{reflist}}

==External links==
* [https://web.archive.org/web/20061207152451/http://biology.clc.uc.edu/courses/bio105/nervous.htm Diagram at clc.uc.edu]
* {{BUHistology|21301loa}}{{snd}}"Ultrastructure of the Cell: myelinated axon and Schwann cell"
* [http://ccdb.ucsd.edu/sand/main?stype=lite&keyword=schwann&Submit=Go&event=display&start=1 Cell Centered Database{{snd}}Schwann cell]

{{Nervous tissue}}
{{Authority control}}

{{DEFAULTSORT:Schwann Cell}}
[[Category:Glial cells]]
[[Category:Neurophysiology]]