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Journal of Neuroscience, Vol 14, 2594-2605, Copyright © 1994 by Society for Neuroscience
The role of oligodendrocytes and myelin on axon maturation in the developing rat retinofugal pathway
RJ Colello, U Pott and ME Schwab
Brain Research Institute, University of Zurich, Switzerland.
In neonatal mammals, newly grown optic axons are uniformly small in
diameter. In the adult, in contrast, axons within the optic nerve can be
classified into distinct groups according to their diameter. Because axon
diameters are also related to the thickness of the myelin sheath, which in
turn determines the velocity of action potential propagation, the question
of what determines the axon diameter is of critical importance. In a
project aimed at determining the influence of the ensheathing cell on axon
maturation, oligodendrocyte development was prevented by eliminating their
precursors by unilateral x-irradiation at birth. Axon diameters in both the
normal and the myelin-free optic nerves were then measured at varying
stages of development. The results demonstrate that axon diameter growth
remained substantially reduced in the absence of oligodendrocytes.
Interestingly, by x-irradiating the optic nerve and tract on one side of
the brain, fibers crossing the chiasm became larger as they went from an
unmyelinated nerve to a myelinated tract; fibers on the nonirradiated side
became smaller as they went from a myelinated nerve and crossed into the
nonmyelinated tract. These results clearly point to a local regulation of
axon diameter by oligodendrocytes. Moreover, ganglion cells measured 9 d
after the initiation of myelination (postnatal day 6, P6) were of similar
size within normal retinas and retinas whose axons were x- irradiated,
suggesting that ganglion cell growth occurs in spite of the lack of myelin
and axon diameter maturation. Finally, we showed, through both section
staining with antibodies to myelin basic protein (MBP) and Northern blot
analysis using a probe to MBP, that the x- irradiated nerve began a delayed
myelination period (in a gradient from chiasm to eye) at P15 and reached an
almost normal myelin pattern at P28. Axons from these nerves grew to
seemingly normal diameter concomitant with this delayed myelination.
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