Oligodendrocytes and the control of myelination in vivo: New insights fromthe rat anterior medullary velum

The rat anterior medullary velum (AMV) is representative of the brain and s pinal cord, overall, and provides an almost two-dimensional preparation for investigating axon-glial interactions in vivo. Here, we review some of our findings on axon-oligodendrocyte unit relations in our adult, development, and injury paradigms: (1) adult oligodendrocytes are phenotypically hetero geneous, conforming to Del Rio Hortega's types I-IV, whereby differences in oligodendrocyte morphology, metabolism, myelin sheath radial and longitudi nal dimensions, and biochemistry correlate with the diameters of axons in t he unit; (2) oligodendrocytes derive from a common premyelinating oligodend rocyte phenotype, and divergence of types I-IV is related to the age they e merge and the presumptive diameter of axons in the unit; (3) during myelina tion, axon-oligodendrocyte units progress through a sequence of maturation phases, related to axon contact, ensheathment, establishment of internodal myelin sheaths, and finally the radial growth and compaction of the myelin sheath; (4) we provide direct in vivo evidence that platelet-derived growth factor-AA (PDGF-AA), fibroblast growth factor (FGF-2), and insulin-like gr owth factor-1 (IGF-I) differentially regulate these events, by injecting th e growth factors into the cerebrospinal fluid of neonatal rat pups; (5) in lesioned adult AMV, transected central nervous system (CNS) axons regenerat e through the putatively inhibitory environment of the glial scar, but remy elination by oligodendrocytes is incomplete, indicating that axon-oligodend rocyte interactions are defective; and (6) in the adult AMV, cells expressi ng the NG2 chondroitin sulphate have a presumptive adult oligodendrocyte pr ogenitor antigenic phenotype, but are highly complex cells and send process es to contact axolemma at nodes of Ranvier, suggesting they subserve a spec ific perinodal function. Thus, axons and oligodendrocyte lineage cells form interdependent functional units, but oligodendrocyte numbers, differentiat ion, phenotype divergence, and myelinogenesis are governed by axons in the units, mediated by growth factors and contact-dependent signals. (C) 2000 W iley-Liss, Inc.