Origins and early development of oligodendrocyte precursor cells

Abstract

Oligodendrocytes, the myelinating cells of the CNS, develop from glial progenitor cells known as 0-2A progenitors (for reviews see 1,2 and 3). 0-2A progenitor cells are so-called because they can differentiate into either oligodendrocytes or type-2 astrocytes in vitro: in medium containing low (≤ 0.5%) fetal calf serum (FCS) they differentiate into oligodendrocytes whereas in 10% FCS they differentiate into type-2 astrocytes (4). 0-2A progenitors and their differentiated progeny can be distinguished in vitro by morphology and by their characteristic antigenic phenotypes. 0-2A progenitors often have a bipolar morphology and label with monoclonal antibody A2B5 (5), which recognizes a specific set of gangliosides, and with antibodies to the NG2 chondroitin sulphate (6). As they mature, 0-2A progenitors become multi-polar, their proliferative and migratory properties change (7 and 8) and they start to express sulphatide and other related antigens that are recognized by monoclonal antibody 04 (9). Differentiated oligodendrocytes have a complex, process-bearing morphology and label specifically with antibodies against galactocerebroside (GC) (10). Type-2 astrocytes are process-bearing cells in vitro that label with antibodies against the glial fibrillary acidic protein (GFAP). After they differentiate, oligodendrocytes lose the A2B5 antigen whereas type-2 astrocytes retain it. The oligodendrocyte differentiation pathway seems to be the default behaviour for 0-2A progenitors because a single progenitor cell differentiates into an oligodendrocyte if it is cultured on its own in defined, low-serum medium in the absence of other cells (11). It is not known what the active ingredient in FCS is that can induce type-2 astrocyte differentiation in vitro, but the activity can be mimicked by pure ciliary neurotrophic factor (CNTF) in collaboration with uncharacterized extracellular matrix components secreted by cultures of cortical astrocytes (12). Despite careful searching, there is still no definitive evidence for the existence of cells with the antigenic phenotype of type-2 astrocytes in vivo (13). Perhaps type-2 astrocytes will eventually turn up in a restricted region(s) of the CNS or under certain pathological conditions. For the present, however, we regard 0-2A progenitors as dedicated oligodendrocyte progenitors in vivo, but retain the prefix 0-2A as a reminder of their differentiation potential in vitro. Figure 1 shows a diagram of the life history of an oligodendrocyte.