Rj. Colello et Me. Schwab, A ROLE FOR OLIGODENDROCYTES IN THE STABILIZATION OF OPTIC AXON NUMBERS, The Journal of neuroscience, 14(11), 1994, pp. 6446-6452
Differentiated oligodendrocytes express neurite growth inhibitory prot
eins at a time when these cells are involved in the myelination of rec
ently formed fiber pathways. As the process of myelination follows the
completion of neurite outgrowth and is concurrent with the stabilizat
ion of fiber numbers in a pathway, we set out to determine whether mye
lination and fiber tract stability could be causally related. Myelin f
ormation was prevented in the rat retinofugal pathway by x-irradiating
the optic nerves during oligodendrocyte proliferation. Electron micro
scopic and immunohistochemical analysis of irradiated optic nerves at
P15 showed that oligodendrocytes and myelin were virtually absent. Opt
ic fiber numbers were determined at 2 weeks of age throughout the leng
th of normal and x-irradiated nerves. In some cases, normal or irradia
tion-treated pups were intraocularly injected with FGF 5 d prior to th
e fiber count in order to promote neurite outgrowth. Axon counts showe
d that the total fiber number in a myelin-free optic nerve was 10-30%
higher than that of a myelinated nerve. Further, fiber numbers fluctua
ted by as much as 20% along the length of a myelin-free nerve but were
relatively constant throughout the length of a myelinated nerve. Trea
tment of myelinated nerves with fibroblast growth factor (FGF) had no
effect on either total fiber numbers or fiber number fluctuation. Conv
ersely, fiber numbers in myelin-free/FGF-treated optic nerves were as
much as 40% higher than in normals. Furthermore, total fiber numbers a
long the length of these nerves fluctuated by up to 34%. These results
indicate that, in the absence of myelination, optic fibers are able t
o form sprouts. This suggests that oligodendrocytes have a role in pre
venting sprouting and stabilizing the number of fibers in a pathway du
ring development.