Oligodendrocytes in Development, Myelin Generation and Beyond

Abstract

Oligodendrocytes are the myelinating cells of the central nervous system (CNS) that are generated from oligodendrocyte progenitor cells (OPC). OPC are distributed throughout the CNS and represent a pool of migratory and proliferative adult progenitor cells that can differentiate into oligodendrocytes. The central function of oligodendrocytes is to generate myelin, which is an extended membrane from the cell that wraps tightly around axons. Due to this energy consuming process and the associated high metabolic turnover oligodendrocytes are vulnerable to cytotoxic and excitotoxic factors. Oligodendrocyte pathology is therefore evident in a range of disorders including multiple sclerosis, schizophrenia and Alzheimer's disease. Deceased oligodendrocytes can be replenished from the adult OPC pool and lost myelin can be regenerated during remyelination, which can prevent axonal degeneration and can restore function. Cell population studies have recently identified novel immunomodulatory functions of oligodendrocytes, the implications of which, e.g., for diseases with primary oligodendrocyte pathology, are not yet clear. Here, we review the journey of oligodendrocytes from the embryonic stage to their role in homeostasis and their fate in disease. We will also discuss the most common models used to study oligodendrocytes and describe newly discovered functions of oligodendrocytes.

Keywords: OPC; multiple sclerosis; myelin; myelination; oligodendrocyte progenitor cells; oligodendrocytes; remyelination.

Figure 1

Schematic depiction of oligodendroglial lineage markers specific for different developmental stages from neuronal progenitor cells (NPC) to myelinating oligodendrocyte (OL). A2B5 recognises progenitor cells, NPC and oligodendrocyte progenitor cells (OPC), while oligodendroglial cell lineage markers Olig1 and 2 as well as Sox10 and Nkx2.2 are expressed in all cells of the lineage, OPC and pre-oligodendrocytes (pre-OL) are characterised by PDGFR-α and NG2 expression. PLP, O4, O1 and CNPase are expressed during transition from progenitor to differentiated oligodendrocytes, while differentiated, axon-myelinating oligodendrocytes are characterised by myelin protein expression (MBP, MAG, MOG, GalC). NPC: neuronal progenitor cell; OPC: oligodendrocyte progenitor cell; OL: oligodendrocyte; PDGFR-α: platelet-derived growth factor receptor A; NG2: neuron-glial antigen 2; PLP: proteolipid protein; CNPase: 2’,3’-Cyclic-nucleotide 3’-phosphodiesterase; MBP: myelin basic protein; MAG: myelin associated glycoprotein; MOG: myelin-oligodendrocyte glycoprotein; GalC: galactocerebroside.

Figure 2

Oligodendrocytes in myelination, demyelination and remyelination. Oligodendrocytes myelinate large diameter axons in the CNS and provide trophic support for the underlying axon. Oligodendrocytes are highly vulnerable and insults such as trauma, immune-mediated attacks or ischaemia can lead to oligodendrocyte death and demyelination. Newly differentiated oligodendrocytes derived from an adult OPC pool can replace deceased oligodendrocytes, which can reinstate the myelin sheath around demyelinated axons (remyelination). Regenerated myelin is thinner than the original myelin sheath.