During development, Schwann cells gradually invest smaller and smaller bundles of axons until a 1:1 relationship is established. Schwann cells then undergo substantial elongation along the axon and secrete the basal lamina. The subsequent interactions between the Schwann cell and the basal lamina regulate its differentiation and myelination. Axon diameter is a key factor determining whether an axon is myelinated; every Schwann cell has the potential to myelinate an axon but does so only if it comes into contact with axons with a critical diameter of 0.7 ^m. Numerous molecules mediate specific aspects of interactions between Schwann cells and axons. NRG-1 promotes Schwann cell proliferation and survival, and inhibits myelination during development. Before the onset of myelination, Schwann cells express NCAM and L1, both of which play roles in recognition between axons and Schwann cells. L1 on axons and integrins on Schwann cells are essential for ensheathment. On the formation of axon-Schwann cell contact, the expression of NCAM and L1 is down-regulated and MAG is expressed, which mediates the initiation of the myelin spiral. Myelination is accompanied by the expression of P0, which is essential for the spiralling of the myelin sheath and adhesion of the myelin lamellae. Periaxin is important in stabilizing the mature myelin sheath by interactions with the basal lamina. Myelin formation is by the progression of the inner cytoplasmic ridge or lip, which spirals under the compacted myelin (this is opposed to the earlier idea that the Schwann cell itself spiralled around the axon). It is likely that myelin deposition proceeds in the same manner in the CNS, although the picture is complicated by the fact that oligodendrocytes myelinate multiple axons. Longitudinal growth establishes the incipient internodal segment at an early stage, and subsequent growth depends on the developmental lengthening of the nerve. The number of lamellae increases in direct relation to the radial growth of the axon. The two events are interdependent and axons do not attain their adult dimensions in the absence of Schwann cells; increased neurofilament phosphorylation depends on Schwann cell-axon interactions involving MAG.
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