• R J Hardy and V L Friedrich.
• Brookdale Center for Molecular Biology, Mount Sinai Medical School, New York, NY 10029, USA.
• Dev. Neurosci. 1996 Jan 1;18(4):243-54.

AbstractMyelin sheaths develop in the central nervous system (CNS) as elaborations of the processes of oligodendrocytes. Although many details of the spiral wrapping of oligodendrocyte processes around axons and their subsequent transformation into myelin sheaths are known from thin-section electron-microscopic studies, the three-dimensional architecture of the myelin-forming cells is incompletely understood. To characterize this aspect of oligodendrocyte development, we labeled thick (100- to 300-microns) sections of developing murine CNS with oligodendrocyte marker antibodies, recorded individual cells in serial optical sections by confocal microscopy, and created whole-cell reconstructions of oligodendrocytes before and during the initiation of myelination. We distinguish three stages in the maturation of oligodendrocytes, which at all three stages are labeled by the O4, O1 and Ranscht monoclonals and by antibodies against the myelin-specific proteins CNP and myelin basic protein. Premyelinating oligodendrocytes, present before axonal ensheathment begins, emit multiple irregular processes which have predominant radial orientation. These processes, which generally terminate within 50 microns of the cell body, have a surface area 3-8 times or more that of the cell body itself and may represent a mechanism for sampling the local environment of each cell and for identifying target axons. Transitional cells have initiated one or more myelin sheaths; these cells progressively reduce the number of their radial processes as they increase the number of their myelin internodes. The radial processes of each transitional cell are most reduced in parts of the process arbor where ensheathment has begun, suggesting directional control in the elaboration or stability of the radial processes. Mature myelin-bearing oligodendrocytes entirely lack the radial processes and instead emit a few sparsely branching processes which connect cell bodies with myelin internodes. Three-dimensional analysis of the earliest stages in myelin sheath formation reveals two distinct phases. The initiating event in the formation of myelin internodes is the growth of thin unbranched processes, termed 'initiator processes', along axons. The second phase, spiral ensheathment of target axons, begins through the elaboration from each initiator process of lamellar extensions which extend circumferentially around the target axon and thereby form the first turn of its myelin sheath.

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