The source of the new population of oligodendrocytes which successfull
y remyelinates experimentally induced demyelination of the cat optic n
erve was studied with a combination of techniques. These included corr
elative light microscopy, immunocytochemistry, electron microscopy and
autoradiography in transverse and longitudinal sections. Extending th
e analysis from the newly generated oligodendrocyte back to the very e
arly demyalinative phase of the lesion enabled the identification of a
glial precursor cell (GPC) outside the lesion which appeared to be re
adily recruitable and motile. This cell is likely to be the product of
the division of a putative resting progenitor cell residing in a cent
ral fascicular location of the normal optic nerve surrounding the lesi
on. On arriving at the fringe of the lesion, GPCs are transformed into
vimentin-positive small glial cells (SGCs) possibly by signals fr om
demyelinated axons to which the SGCs become closely apposed. Small gli
al cells, which together with GPCs share several features in common wi
th 0-2A perinatal progenitors of the rodent optic nerve, then differen
tiate into oligodendrocytes. Together these findings suggest that the
events leading to remyelination of adult mammalian optic nerve commenc
e soon after the demyelinating injury and might recapitulate the princ
ipal events of developmental myelinogenesis.