A direct role for neurons in CNS myelination has yet to be demonstrate
d. CNS myelination can be examined in cerebellar slice cultures, which
faithfully reproduce both synthesis and wrapping of myelin. In an att
empt to demonstrate a role for axolemma in this process, we generated
more than 2000 axolemma-reactive monoclonal antibodies. One clone, G21
.3, repeatedly blocked myelination in cerebellar slices, as documented
by both biochemistry and morphology. The antibody caused a dramatic r
eduction in myelin lipid and protein synthesis. CNS white matter, scia
tic nerve, and neuronal cultures were positively stained with G21.3, w
hereas oligodendrocytes and myelin were fully negative. The antibody i
dentified a restricted number of proteins in purified axolemma. These
results suggest a direct involvement of axons in CNS myelination.