In order to study the signals that control the onset of myelination, we coc
ultured highly purified postnatal retinal ganglion cells and optic nerve ol
igodendrocytes under serum-free conditions that promote their survival for
at least a month and found that no myelination occurred. Although the addit
ion of optic nerve astrocytes induced the oligodendrocyte processes to alig
n with, and adhere to, axons, myelination still did not occur. The effect o
f astrocytes was mimicked by removal of polysialic acid from both cell type
s using neuroaminidase. These findings provide evidence for a novel role fo
r astrocytes in controlling the onset of myelination by promoting adhesion
of oligodendrocyte processes to axons. They also suggest that other, as yet
unidentified, cell-cell interactions are necessary to induce the myelinati
on process itself.