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In order to determine the signals that initiate axon myelination in the CNS, we have chronicled the differentiation of oligodendrocytes in the rat optic nerve and related this to the time course and spatial gradient seen for optic axon myelination. By using markers specific to the varying stages of oligodendrocyte differentiation we found that oligodendrocyte progenitor cells, present throughout the length of the nerve at postnatal day 2, mature into GC+ oligodendrocytes in a chiasm to eye progression. This gradient along the nerve of oligodendrocyte differentiation continues with oligodendrocytes near the chiasm expressing the genes and encoded proteins to MBP and PLP 3 d before oligodendrocytes near the eye. Although oligodendrocyte differentiation and maturation occurs in a chiasm to eye gradient along the nerve, optic axon segments near the eye are ensheathed with myelin before segments near the chiasm. This suggests that the myelination of optic axons is initiated by a signaling step that is independent of oligodendrocyte differentiation and is stronger near the eye than the chiasm region of the nerve. By examining proposed axonal signals, we found that the onset of myelination is independent of the electrical activity of an axon but can be correlated to the size of an axon.

The chronology of oligodendrocyte differentiation in the rat optic nerve: evidence for a signaling step initiating myelination in the CNS