The oligodendrocyte is the myelin-forming cell in the central nervous system. Despite the close interaction between axons and oligodendrocytes, there is little evidence that neurons influence myelinogenesis. On the contrary, newly differentiated oligodendrocytes, which mature in culture in the total absence of neurons, synthesize the myelinspecific constituents of oligodendrocytes differentiated in vivo and even form myelin-like figures. Neuronal To determine whether the onset of myelination was the consequence only of oligodendrocyte maturation or depended on an axonal signal, we investigated the influence of axonal electrical activity on myelinogenesis. Indeed, action potentials have been demonstrated to play a key role during CNS development, particularly in the visual system (20,21). Here we show that inhibition of electrical activity with the specific Na+ channel blocker tetrodotoxin (TTX) prevents the initiation of myelinogenesis in a system of in vitro myelination using dissociated cultures from embryonic brain and in vivo, in the optic nerve. In addition, with K+ that blocks action potentials by maintaining the cells in a depolarized state, or a-scorpion toxin (a-ScTX), which induces repetitive electrical activity by slowing Na+ channel inactivation, we provide evidence that it is the action potential itself which is responsible for the onset of myelination.

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Products of the PLP gene, proteolipid protein and its isoform DM-20, are the most abundant proteins in CNS myelin, and are markers of the oligodendrocyte, the myelin-forming cell in the CNS. The DM-20 transcript has previously been reported to be expressed in newborn oligodendrocyte progenitor cells and during embryonic development. We have therefore used a DM-20 cRNA probe to follow, by in situ hybridization, the oligodendrocyte lineage during embryonic development. DM-20-expressing cells were first detected at E9.5 in the ventricular germinal layer of the laterobasal plate of the diencephalon. At E14.5, DM-20+ cells had largely disappeared from the diencephalic ventricular germinal layer and had colonized the ventral mantle layer at the posterior part of the basal diencephalon. Between E17.5 and P1, the number of DM-20+ cells increased and progressively invaded the major white matter tracts. In the hindbrain, DM-20+ cells appeared at E12.5 in the caudal part of the rhombencephalon, and at E14.5 all along the ventral spinal cord. Between E14.5 and P1, DM-20+ cells progressively colonized, first ventrally then dorsally, all the spinal cord and more extensively the white matter tracts. At E14.5, a large gap separated, rostrally, the medullary columns from the mantle layer cells in the prosencephalon, suggesting that oligodendrocytes in the mid- and forebrain originate from a different pool of precursors than in the rhombencephalon and the spinal cord. Together, these observations suggest that expression of the DM-20 transcript is an early marker of commitment to the oligodendrocyte lineage, and that oligodendrocyte precursors originate in a ventrally restricted region.