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

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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+, PDGFαR+, 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 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNPase).