Myelin sheath formation is initiated when the Schwann cell mesaxon surrounds the axon. A sheetlike extension of the mesaxon then wraps around the axon in a spiraling motion. The first few layers or lamellae of the spiral are not compactly
FIGURE 12.9 • Photomicrographs of a peripheral nerve in cross and longitudinal sections. a. Photomicrograph of an osmium-fixed, toluidine blue–stained peripheral nerve cut in cross-section. The axons (A) appear clear. The myelin is represented by the dark ring surrounding the axons. Note the variation in diameter of the individual axons. In some of the nerves, the myelin appears to consist of two separate rings (asterisks). This is caused by the section passing through a Schmidt-Lanterman cleft. Epi, epineurium. 640. b. Photomicrograph showing longitudinally sectioned myelinated nerve axons (A) in the same preparation as above. A node of Ranvier (NR) is seen near the center of the micrograph. In the same axon, a Schmidt-Lanterman cleft (SL) is seen on each side of the node. In addition, a number of Schmidt-Lanterman clefts can be seen in the adjacent axons. The perinodal cytoplasm of the Schwann cell at the node of Ranvier and the Schwann cell cytoplasm at the Schmidt-Lanterman cleft appear virtually unstained. 640.
FIGURE 12.10 • Diagram showing successive stages in the formation of myelin by a Schwann cell. a. The axon initially lies in a groove on the surface of the Schwann cell. b. The axon is surrounded by a Schwann cell. Note the two domains of the Schwann cell, the adaxonal plasma-membrane domain and abaxonal plasma-membrane domain. The mesaxon plasma membrane links these domains. The mesaxon membrane initiates myelination by surrounding the embedded axon. c. A sheetlike extension of the mesaxon membrane then wraps around the axon, forming multiple membrane layers. d. During the wrapping process, the cytoplasm is extruded from between the two apposing plasma membranes of the Schwann cell, which then become compacted to form myelin. The outer mesaxon represents invaginated plasma membrane extending from the abaxonal surface of the Schwann cell to the myelin. The inner mesaxon extends from the adaxonal surface of the Schwann cell (the part facing the axon) to the myelin. The inset shows the major proteins responsible for compaction of the myelin sheath. MBP, myelin basic protein; Nrq1, neurorequlin; P0, protein 0; PMP22, peripheral myelin protein of 22 kilodaltons.
arranged—that is, some cytoplasm is left in the first few concentric layers (Fig. 12.10c). The TEM reveals the presence of a 12to 14-nm gap between the outer (extracellular) leaflets and the Schwann cell cytoplasm that separates the inner (cytoplasmic) leaflets. As the wrapping progresses, cytoplasm is squeezed out from between the membrane of the concentric layers of the Schwann cell.
External to, and contiguous with, the developing myelin sheath is a thin outer collar of perinuclear cytoplasm called the sheath of Schwann. This part of the cell is enclosed by an abaxonal plasma membrane and contains the nucleus and most of the organelles of the Schwann cell. Surrounding the Schwann cell is a basal or external lamina. The apposition of the mesaxon of the last layer to itself as it closes the ring of the spiral produces the outer mesaxon, the narrow intercellular space adjacent to the external lamina. Internal to the concentric layers of the developing myelin sheath is a narrow inner collar of Schwann cell cytoplasm surrounded by the adaxonal plasma membrane. The narrow intercellular space between mesaxon membranes communicates with the adaxonal plasma membrane to produce the inner mesaxon (Fig. 12.10d).