Oligodendrocyte specification and differentiation, leading to myelin components for CNS (Homo sapiens)
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Description
Overview of synthesis of components for myelin sheath of the CNS in oligodendrocytes. From [Miron et al, 2011, Figure 1D]: Multi-potent neural stem cells (nestin+) are specified into oligodendrocyte progenitor cells (OPCs; A2B5+, PDGF-alpha-R+, and NG2+) by exposure to sonic hedgehog (SHH) and fibroblast growth factor (FGF), whereas bone morphogenic proteins (BMPs) inhibit this specification. This specification involves the transcription factors Olig2, Nkx2.2, Mash1, MyT1, Nkx2.6, Gli2, and Sox 8/9/10. OPCs can differentiate into multiple cell types including astrocytes, neurons, and Schwann cells. Differentiation along the oligodendroglial lineage to pre-oligodendrocytes/immature oligodendrocytes (O4+/GalC+) is potentiated by the growth factor IGF-1, the cytokine CNTF, and the thyroid hormone T3, and requires the transcription factors Olig1/2, Sox10, and Nkx2.2/2.6. Conversely, BMPs and transcription factors Sox5/6 prevent this differentiation. Differentiation into mature oligodendrocytes is associated with acquisition of myelin-related proteins, such as myelin basic protein (MBP), myelin-associated glycoprotein (MAG), myelin oligodendrocyte glycoprotein (MOG), oligodendrocyte myelin glycoprotein (OMgp), and CNPase.
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- Miron VE, Kuhlmann T, Antel JP; ''''; , PubMed Europe PMC Scholia
- 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
- 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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External references
DataNodes
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| Name | Type | Database reference | Comment |
|---|---|---|---|
| BMP2 | Protein | P12643 (Uniprot-TrEMBL)  | bone morphogenic proteins |
| BMP4 | Protein | P12644 (Uniprot-TrEMBL) | bone morphogenic proteins |
| CNPase | Protein | P09543 (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. |
| CNTF | Protein | P26441 (Uniprot-TrEMBL) | |
| CXCL1 | Protein | P09341 (Uniprot-TrEMBL) | |
| CXCL2 | GeneProduct | P19875 (Uniprot-TrEMBL) | |
| Cerebrosides 22,7% | Metabolite | CHEBI: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% | Metabolite | CHEBI:16113 (ChEBI) | |
| Cholesterol synthesis | Pathway | WP197 (WikiPathways) | |
| FGF | Protein | A0A087WUF6 (Uniprot-TrEMBL) | |
| Gli2 | Protein | P10070 (Uniprot-TrEMBL) | |
| Glycerophospholipid Biosynthetic Pathway | Pathway | WP2533 (WikiPathways) | |
| IGF-1 | Protein | P05019 (Uniprot-TrEMBL) | |
| IL1b | Protein | P01584 (Uniprot-TrEMBL) | |
| LIF | Protein | P15018 (Uniprot-TrEMBL) | |
| Lecithins 11,2% | Metabolite | CHEBI:61995 (ChEBI) | |
| MAG | Protein | P20916 (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. |
| MBP | Protein | A8MZH3 (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. |
| MOG | Protein | Q16653 (Uniprot-TrEMBL) | MOG: myelin oligodendrocyte glycoprotein |
| Mash1 | Protein | P50553 (Uniprot-TrEMBL) | |
| MyT1 | Protein | Q01538 (Uniprot-TrEMBL) | |
| Nkx-2.2 | Protein | O95096 (Uniprot-TrEMBL) | |
| Nkx-2.6 | Protein | A6NCS4 (Uniprot-TrEMBL) | |
| OMG | Protein | P23515 (Uniprot-TrEMBL) | OMgp: oligodendrocyte-meylin glycoprotein |
| Olig1 | Protein | Q8TAK6 (Uniprot-TrEMBL) | |
| Olig2 | Protein | Q13516 (Uniprot-TrEMBL) | |
| PDGF | Protein | P01127 (Uniprot-TrEMBL) | |
| PLP1 | Protein | P60201 (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. |
| Phosphatidylcholine | Metabolite | CHEBI:16110 (ChEBI) | |
| Phosphatidylserine 4,8% | Metabolite | CHEBI:18303 (ChEBI) | |
| SHH | Protein | Q15465 (Uniprot-TrEMBL) | Sonic Hedgehog |
| SOX-10 | Protein | P56693 (Uniprot-TrEMBL) | |
| SOX-5 | Protein | P35711 (Uniprot-TrEMBL) | |
| SOX-6 | Protein | P35712 (Uniprot-TrEMBL) | |
| SOX-8 | Protein | P57073 (Uniprot-TrEMBL) | |
| SOX-9 | Protein | P48436 (Uniprot-TrEMBL) | |
| Sphingolipid metabolism | Pathway | WP1422 (WikiPathways) | |
| Sphingomyelin 7,9% | Metabolite | CHEBI:17636 (ChEBI) | |
| Sulfatide 3,8% | Metabolite | CHEBI:18318 (ChEBI) | |
| T3 | Metabolite | CHEBI:18258 (ChEBI) | |
| TNFa | Protein | P01375 (Uniprot-TrEMBL) | |
| bFGF | Protein | P09038 (Uniprot-TrEMBL) | |
| ethanolamine phosphatides 15,6% | Metabolite | ||
| phosphatidic acid | Metabolite | CHEBI:16337 (ChEBI) | |
| phosphatidylethanolamines | Metabolite | CHEBI:16038 (ChEBI) | |
| phosphatidylinositol | Metabolite | CHEBI:18179 (ChEBI) |
Annotated Interactions
No annotated interactions
