To analyze the expression of cell-surface molecules on neurons or glia during myelination, we have developed a xenotypic coculture system in which mouse oligodendrocytes interact with rat dorsal root ganglion neurons. The axo-glial interactions in these cultures promote oligodendrocyte precursor cell proliferation, survival, and differentiation as in vivo, thus supporting the validity of the xenocultures as a model system to study myelination in which the molecules on the neurons or the glia can be distinguished using species-specific antibodies. We examined the expression of integrins, the major family of cell-surface extracellular matrix receptors, on oligodendrocytes during the early stages of myelination and found that, unlike Schwann cells, oligodendrocytes do not express alpha 6 beta 4 in association with myelin sheath formation. The pattern of integrin expression observed on oligodendrocytes in these cultures is similar to that seen in oligodendrocytes that differentiate in purified cultures, and it comprises alpha 6 beta 1, alpha v beta 5, and an as yet uncharacterized alpha v-associated beta subunit of 80 kDa. Changes in integrin expression associated with differentiation, therefore, do not depend on axonal contact, and beta 4 is not required for myelin sheath formation, although its expression may contribute to the individual properties of oligodendrocytes and Schwann cells.