Oligodendrocyte specification and differentiation, leading to myelin components for CNS (Homo sapiens)

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1, 23Removal of myelin debris andinflammatory factorsSchwann cellOPC differentiationUpregulation of:Chemotactic migrationLegend:NeuronSpecification and differentiationTranscription factor upregulationActivationDifferentiation,RemyelinationAffected Myelin(with lesion)Activitation ofTranscription factorsAstrocyteLecithin consists of:Necessary stimulationAcquisition of myelin related proteinsMajor myelin proteins 30% of dry weightOPC specificationFGFOlig2PDGFphosphatidylethanolaminesCholesterol 27%MOGMetaboliteIGF-1PathwayProteinOlig1Cholesterol synthesisIL1bGlycerophospholipid Biosynthetic PathwaySOX-5MBPOMGPhosphatidylserine 4,8%MAGPLP1CNPase2Major myelin lipids 70% of dry weightCerebrosides 22,7%Sulfatide 3,8%ethanolamine phosphatides 15,6%Lecithins 11,2%Sphingomyelin 7,9%Sphingolipid metabolismphosphatidylinositolPhosphatidylcholinephosphatidic acidOligodendrocyte progenitor cells(A2B5+, PDGF-alpha-R+, NG2+)Mature oligodendrocyte (capable of Myelination)Pre- & Immature- oligodendrocyte(O4+,GalC+)Multi-potent neural stem cell(nestin+)SHHCNTFT3Transcription factor upregulationNkx-2.2Mash1MyT1Nkx-2.6Gli2SOX-8SOX-9SOX-10Olig2Nkx-2.2Nkx-2.6SOX-10Oligodendrocyte progenitor cells(A2B5+, PDGF-alpha-R+)SOX-6BMP4bFGFCXCL1TNFaLIFOlig2Nkx-2.2RemyelinationInflamationPre- & Immature- oligodendrocyteMature oligodendrocyte (capable of Myelination)IL1bTNFaCXCL2BMP2BMP4BMP23Inhibition3


Overview of synthesis of components for myelin sheath of the CNS in oligodendrocytes. "Multi-potent neural stem cells are specified into oligodendrocyte progenitor cells. OPCs can differentiate into multiple cell types including astrocytes, neurons, and Schwann cells. Differentiation along the oligodendroglial lineage to pre-oligodendrocytes/immature oligodendrocytes is potentiated by the growth factor IGF-1, the cytokine CNTF, and the thyroid hormone T3, and requires several transcription factors. BMPs can inhibit this step, as well as the previous one. Differentiation into mature oligodendrocytes is associated with acquisition of myelin-related proteins." Rephrased from [Miron et al, 2011, Figure 1C+D].

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  1. Miron VE, Kuhlmann T, Antel JP; ''''; , PubMed Europe PMC Scholia
  2. Morell P, Quarles RH, Siegel GJ, Agranoff BW, Albers RW, et al.,; ''Charecterisctic Composition of Myelin''; Basic Neurochemistry: Molecular, Cellular and Medical Aspects; https://www.ncbi.nlm.nih.gov/books/NBK28221/, 1999
  3. Cheng X, Wang Y, He Q, Qiu M, Whittemore SR, Cao Q; ''Bone morphogenetic protein signaling and olig1/2 interact to regulate the differentiation and maturation of adult oligodendrocyte precursor cells.''; Stem Cells, 2007 PubMed Europe PMC Scholia


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129364view09:39, 27 March 2024MkutmonOntology Term : 'regulatory pathway' added !
123411view11:12, 25 July 2022EgonwMade three pathways clickable
119229view18:50, 22 June 2021FinterlyAdded ISBN for book citation, removed duplicate Biopax and updated BiopaxRef
116458view10:02, 7 May 2021EweitzModified title
112156view18:00, 29 September 2020Khanspersremoved extraneous text from comment
111634view05:18, 1 September 2020EgonwModified title
107559view14:40, 21 October 2019DeSlAdded legend for clarity
97966view22:35, 27 June 2018Jessev1993changed lay-out
97868view11:28, 12 June 2018DeSlConnecte dunconnected lines.
97867view11:25, 12 June 2018DeSlChanged title+description
97847view08:39, 11 June 2018Jessev1993Added information of inhibition by BMP
97724view09:40, 7 June 2018DeSlModified description
97723view09:39, 7 June 2018DeSlReverted to version '09:31, 7 June 2018' by DeSl
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97714view08:53, 7 June 2018DeSlMore info in comments, added 3 cell types which where missing before.
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97687view15:11, 1 June 2018EgonwReplaced secondary ChEBI identifiers with primary identifiers.
97683view14:39, 1 June 2018EgonwFixed a small mistyping.
97668view07:56, 1 June 2018Jessev1993
97667view07:43, 1 June 2018Jessev1993Ontology Term : 'glial cell' added !
97666view07:43, 1 June 2018Jessev1993Ontology Term : 'myelin accumulating cell' added !
97665view07:43, 1 June 2018Jessev1993Ontology Term : 'oligodendrocyte precursor cell' added !
97664view07:42, 1 June 2018Jessev1993Ontology Term : 'oligodendrocyte' added !
97663view07:26, 1 June 2018Jessev1993New pathway

External references


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NameTypeDatabase referenceComment
BMP2ProteinP12643 (Uniprot-TrEMBL) bone morphogenic proteins
BMP4ProteinP12644 (Uniprot-TrEMBL) bone morphogenic proteins
CNPaseProteinP09543 (Uniprot-TrEMBL) May participate in RNA metabolism in the myelinating cell, CNP is the third most abundant protein in central nervous system myelin. CNPase: 2',3'-cyclic nucleotide 3'phosphodiesterase.
CNTFProteinP26441 (Uniprot-TrEMBL)
CXCL1ProteinP09341 (Uniprot-TrEMBL)
CXCL2GeneProductP19875 (Uniprot-TrEMBL)
Cerebrosides 22,7%MetaboliteCHEBI:23079 (ChEBI) Even though there are no absolute myelin-specific lipids, cerebroside, also known as galactosylceramide, is the most typical of myelin. The concentration of cerebroside in brain is directly proportional to the amount of myelin present. Cerebroside is not required for myelin formation but plays an important role in its insulating capacity and stability.
Cholesterol 27%MetaboliteCHEBI:16113 (ChEBI)
Cholesterol synthesisPathwayWP197 (WikiPathways)
FGFProteinA0A087WUF6 (Uniprot-TrEMBL)
Gli2ProteinP10070 (Uniprot-TrEMBL)
Glycerophospholipid Biosynthetic PathwayPathwayWP2533 (WikiPathways)
IGF-1ProteinP05019 (Uniprot-TrEMBL)
IL1bProteinP01584 (Uniprot-TrEMBL)
LIFProteinP15018 (Uniprot-TrEMBL)
Lecithins 11,2%MetaboliteCHEBI:61995 (ChEBI)
MAGProteinP20916 (Uniprot-TrEMBL) Adhesion molecule that mediates interactions between myelinating cells and neurons by binding to neuronal sialic acid-containing gangliosides and to the glycoproteins RTN4R and RTN4RL2 (By similarity). Not required for initial myelination, but seems to play a role in the maintenance of normal axon myelination. MAG: myelin associated glycoprotein.
MBPProteinA8MZH3 (Uniprot-TrEMBL) The classic group of MBP isoforms are the most abundant protein components of the myelin membrane in the CNS. They have a role in both its formation and stabilization. MBP: myelin basic protein.
MOGProteinQ16653 (Uniprot-TrEMBL) MOG: myelin oligodendrocyte glycoprotein
Mash1ProteinP50553 (Uniprot-TrEMBL)
MyT1ProteinQ01538 (Uniprot-TrEMBL)
Nkx-2.2ProteinO95096 (Uniprot-TrEMBL)
Nkx-2.6ProteinA6NCS4 (Uniprot-TrEMBL)
OMGProteinP23515 (Uniprot-TrEMBL) OMgp: oligodendrocyte-meylin glycoprotein
Olig1ProteinQ8TAK6 (Uniprot-TrEMBL)
Olig2ProteinQ13516 (Uniprot-TrEMBL)
PDGFProteinP01127 (Uniprot-TrEMBL)
PLP1ProteinP60201 (Uniprot-TrEMBL) This is the major myelin protein from the central nervous system. It plays an important role in the formation or maintenance of the multilamellar structure of myelin.
PhosphatidylcholineMetaboliteCHEBI:16110 (ChEBI)
Phosphatidylserine 4,8%MetaboliteCHEBI:18303 (ChEBI)
SHHProteinQ15465 (Uniprot-TrEMBL) Sonic Hedgehog
SOX-10ProteinP56693 (Uniprot-TrEMBL)
SOX-5ProteinP35711 (Uniprot-TrEMBL)
SOX-6ProteinP35712 (Uniprot-TrEMBL)
SOX-8ProteinP57073 (Uniprot-TrEMBL)
SOX-9ProteinP48436 (Uniprot-TrEMBL)
Sphingolipid metabolismPathwayWP1422 (WikiPathways)
Sphingomyelin 7,9%MetaboliteCHEBI:17636 (ChEBI)
Sulfatide 3,8%MetaboliteCHEBI:18318 (ChEBI)
T3MetaboliteCHEBI:18258 (ChEBI)
TNFaProteinP01375 (Uniprot-TrEMBL)
bFGFProteinP09038 (Uniprot-TrEMBL)
ethanolamine phosphatides 15,6%Metabolite
phosphatidic acidMetaboliteCHEBI:16337 (ChEBI)
phosphatidylethanolaminesMetaboliteCHEBI:16038 (ChEBI)
phosphatidylinositolMetaboliteCHEBI:18179 (ChEBI)

Annotated Interactions

No annotated interactions

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