Cells and Signaling in Oligodendrocyte Development

The myelin-synthesizing oligodendrocyte is compromised in many neuropathological diseases, including demyelinating diseases (e.g. multiple sclerosis), metabolic diseases (e.g. Pelizaeus-Merzbacher), infectious diseases (e.g. progressive multifocal leukoencephalopathy), neurodegenerative diseases (e.g. multisystem degeneration), and possibly neoplasms (e.g. oligodendrogliomas). Understanding the development of the oligodendrocyte has important implications for both the pathogenesis of these diseases and also potential therapy. Over the past 20 yr, research in oligodendrocyte development has delineated a pathway from progenitors to mature oligodendrocytes. In fact, the oligodendrocyte has served as a model for lineage development in part due to the identification of specific phenotypic stages during maturation. From this has come the identification of numerous signaling molecules that instruct oligodendrocyte development. More recently, transgenic and targeted mutagenesis studies have begun to identify new factors involved in oligodendrocyte development and have questioned some of the older observations. This review will attempt to update the current state of research on the progression of the oligodendrocyte lineage. Oligodendrocytes develop from proliferating precursor cells migrating out of germinal zones in the brain and spinal cord. When the cells reach their final destination in the brain parenchyma, they become postmitotic, extend processes, and begin to synthesize the components of myelin as extensions of their plasma membranes. In most animals, this occurs relatively late in CNS development during late embryonic and early postnatal life, after neurons and astrocytes are formed. This myelin forms an insulating sheath around axons, serving dual functions in the nervous system. Historically, myelin was recognized as critical because it facilitates rapid propagation of nervous impulses through very small spaces, thus permitting axons to be of small caliber (1). More recently, myelin has been found to modulate axonal structure and support axonal integrity, as well (2). The oligodendrocyte has become a model CNS cell type for the study of lineage development due …