Mechanisms of oligodendrocyte commitment in the vertebrate CNS

The vertebrate CNS contains many di€erent types of neurons and glia. These distinct cells develop from the neuroepithelial cells of the neural tube in de®ned temporal and spatial patterns. Recent studies have begun to de®ne the signals that regulate commitment to speci®c neuronal and glial phenotypes. Macroglial cells encompass two major cell types; astrocytes and oligodendrocytes. Astrocytes are a heterogeneous family of cells that share several characteristics such as the expression of glial ®brillary acid protein (GFAP) immunoreactive intermediate ®laments at some time during their development. The proposed functions of astrocytes are also diverse. During development, astrocytes or their precursors are thought to support axon outgrowth and are utilized as cellular sca€olds for neuronal migration. In the adult, astrocytes contribute to blood brain barrier formation, form glial scars after injury and may mediate neuronal survival and death through modulation of neurotransmitter levels. In contrast to the diversity among astrocytes, oligodendrocytes appear to be a relatively homogenous population of cells. In white matter the primary role of oligodendrocytes is to form myelin, the fatty insulation around large diameter axons that facilitates rapid saltatory conduction of electrical impulses. Although there is little myelin in gray matter there are a large number of oligodendrocytes and their precursors. The role of oligodendrocytes in gray matter is not clear. It may be these cells provide trophic support to the local neurons or act as a reserve to replace oligodendrocytes lost during normal turnover in the mature CNS. Indeed, in vitro studies have identi®ed oligodendrocyte lineage cells with a high proliferative capacity that can be isolated from mature CNS tissue.