The maturation of oligodendrocyte precursors into myeli-nating oligodendrocytes occurs at different times in different fiber tracts during development. A general principle is that myelination of fiber tracts begins with the phylogenetically oldest fiber tracts. Hence, myelination of motor and sensory fiber roots and cerebellar peduncles precedes association with cortical areas. This pattern is dramatically illustrated in the human, wherein motor and sensory roots in the PNS begin myelination as early as the fourth fetal month and is completed within several months after birth, whereas association areas are still being myelinated into the third decade (90). Another rule of thumb is that myelination proceeds rostrocaudally in the spinal cord but caudorostrally in the brainstem. In the mouse, myelination begins in the ventral funiculi at birth, in the optic nerve 5 days postnatally (Figure 2.6), and in the corpus callosum approximately 14 days postnatally. Although gradients of myelination can be ascribed to different regions of the brain and spinal cord, the gradient is not precisely tuned and can differ from one species to another. In optic nerves of rats, myelination proceeds from the optic nerve head at the retina toward the chiasm (91-92). In optic nerves of rabbits, the pattern of myeli-nation is more homogeneous than in the rat (92). In both species, myelination is retarded near the optic canal, indicating that local factors modulate myelination along axons. Interestingly, the first myelinated fibers were found adjacent to blood vessels, suggesting factors from the vascular system accelerate oligodendrocyte differentiation (92).
After migration from the ventricular and subven-tricular zones into the presumptive white and gray matter, the oligodendrocytic precursors undergo a dramatic change in their morphology from bipolar cells to snowflake-shaped cells with multiple radial processes (Figure 2.7A). These snowflake-shaped cells completely blanket the neuropil, such that their processes are likely to be in direct contact with all axons contained within their sphere. The premyelinating cells already express most myelin proteins including MBP (Figure 2.7A) and glycolipids including galactocerebroside and sulfatide (93). These observations indicate that an intrinsic genetic program in oligodendrocytes activates myelin gene expression. The axons "selected" for myelination by an oligodendrocyte are not necessarily the axons closest to the cell body, and all axons touched by oligodendrocyte processes are not ensheathed. The oligodendrocyte shown in Figure 2.7B extends processes to two bundles of fibers on opposite sides of the cell body. This static picture may at first glance give the impression that specific trophic stimuli from axons have persuaded the oligodendrocyte to send processes to these bundles. However, it is likely that the radial processes of the oligo-
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