MOLECULAR-BASES OF MYELIN FORMATION AS REVEALED BY INVESTIGATIONS ON MICE DEFICIENT IN GLIAL-CELL SURFACE MOLECULES

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 in strumental in understanding the role of these molecules during the for mation of the spiraling loops around the axon, compaction of the spira ling loops, determination of the thickness of the myelin sheath, and m yelin maintenance. In the PNS, the major peripheral myelin protein PO and the peripheral myelin protein (PMP) 22 are involved in spiral form ation as reflected by retarded myelin formation in mice deficient for the respective molecules. An involvement of the myelin-associated glyc oprotein (MAG) in this process is detectable only in mice deficient in both PO and MAG, suggesting that PO can replace MAG during the format ion of the spiraling loops. Myelin compaction is mediated by both PO a nd the intracellular myelin component myelin basic protein (MBP). The determination of the correct myelin thickness is mediated by PO, MBP, and PMP22, with PO and MBP fostering and PMP22 attenuating myelin grow th. For the maintenance of the association of the Schwann cell and mye lin with its ensheathed axon, the myelin components PO, PMP22, MAG, an d 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. Myeli n compaction is mediated by MBP and by PLP, which fulfills some analog ous functions in the CNS as PO in the PNS. These studies reveal that m yelin-related cell surface molecules can play distinct but also partia lly overlapping roles during the formation and maintenance of myelin. (C) 1997 Wiley-Liss, Inc.