Molecular bases of myelin formation as revealed by investigations on mice deficient in glial cell surface molecules

Abstract

Several glia-associated cell surface molecules have been implicated in myelin formation in the central (CNS) and peripheral nervous system (PNS). Recent studies in mice deficient for such molecules have been instrumental in understanding the role of these molecules during the formation of the spiraling loops around the axon, compaction of the spiraling loops, determination of the thickness of the myelin sheath, and myelin maintenance. In the PNS, the major peripheral myelin protein P0 and the peripheral myelin protein (PMP) 22 are involved in spiral formation as reflected by retarded myelin formation in mice deficient for the respective molecules. An involvement of the myelin-associated glycoprotein (MAG) in this process is detectable only in mice deficient in both P0 and MAG, suggesting that P0 can replace MAG during the formation of the spiraling loops. Myelin compaction is mediated by both P0 and the intracellular myelin component myelin basic protein (MBP). The determination of the correct myelin thickness is mediated by P0, MBP, and PMP22, with P0 and MBP fostering and PMP22 attenuating myelin growth. For the maintenance of the association of the Schwann cell and myelin with its ensheathed axon, the myelin components P0, PMP22, MAG, and Connexin 32 are crucial. In the CNS, recognition of oligodendrocytes and axons and the formation of the spiraling loops is mediated by MAG. MAG is additionally responsible for the maintenance of myelin. Myelin compaction is mediated by MBP and by PLP, which fulfills some analogous functions in the CNS as P0 in the PNS. These studies reveal that myelin-related cell surface molecules can play distinct but also partially overlapping roles during the formation and maintenance of myelin. GLIA 19:298–310, 1997. © 1997 Wiley-Liss, Inc.