Immunoelectron microscopic localization of neural cell adhesion molecules (L1, N-CAM, and MAG) and their shared carbohydrate epitope and myelin basic protein in developing sciatic nerve.

Abstract

Abstract. The cellular and subcellular localization of the neural cell adhesion molecules L1, N-CAM, and myelin-associated glycoprotein (MAG), their shared carbohydrate epitope L2/HNK-1, and the myelin basic protein (MBP) were studied by pre-and postembedding immunoelectron microscopic labeling procedures in developing mouse sciatic nerve. L1 and N-CAM showed a similar staining pattern. Both were localized on small, non-myelinated, fasciculating axons and axons ensheathed by non-myelinating Schwann cells. Schwann cells were also positive for L1 and N-CAM in their non-myelinating state and at the onset of myelination, when the Schwann cell processes had turned ~1.5 loops. Thereafter, neither axon nor Schwann cell could be detected to express the L1 antigen, whereas N-CAM was found in the periaxonal area and, more weakly, in compact myelin of myelinated fibers. Compact myelin, Schmidt-Lanterman incisures, paranodal loops, and finger-like processes of Schwann cells at nodes of Ranvier were Ll-negative. At the nodes of Ranvier, the axolemma was also always L1-and N-CAM-negative. The L2/HNK-1 carbohydrate epitope coincided in its cellular and subcellular localization most closely to that observed for L1. MAG appeared on Schwann cells at the time L1 expression ceased. MAG was then expressed at sites of axon-myelinating Schwann cell apposition and noncompacted loops of developing myelin. When compaction of myelin occurred, MAG remained present only at the axon-Schwann cell interface; Schmidt-Lanterman incisures, inner and outer mesaxons, and paranodal loops, but not at finger-like processes of Schwann cells at nodes of Ranvier or compacted myelin. All three adhesion molecules and the L2/HNK-1 epitope could be detected in a nonuniform staining pattern in basement membrane of Schwann cells and collagen fibrils of the endoneurium. MBP was detectable in compacted myelin, but not in Schmidt-Lanterman incisures, inner and outer mesaxon, paranodal loops, and finger-like processes at nodes of Ranvier, nor in the periaxonal regions of myelinated fibers, thus showing a complementary distribution to MAG. These studies show that axonSchwann cell interactions are characterized by the sequential appearance of cell adhesion molecules and MBP apparently coordinated in time and space. From this sequence it may be deduced that L1 and N-CAM are involved in fasciculation, initial axon-Schwann cell interaction, and onset of myelination, with MAG to follow and MBP to appear only in compacted myelin. In contrast to L1, N-CAM may be further involved in the maintenance of compact myelin and axon-myelin apposition of larger diameter axons.URING development of peripheral nerves, cell-to-cell interactions follow a sequence of events that involve surface contacts of axons with the mesenchymal environment and peripheral glia, the Schwann cells, which are derived from the neural crest. Proliferating Schwann cells have been observed to migrate along outgrowing axons of peripheral nerves and withdraw from the mitotic cycle to form the myelin sheath or...

Distribution of CD9 in the developing and mature rat nervous system

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Upregulation of the Endosomal-Lysosomal Pathway in the Trembler-J Neuropathy

“…In the normal nerve, MAG is found in the periaxonal region of the myelin sheath and in areas of uncompacted myelin, such as Schmidt-Lanterman incisures and the paranodes (Fig. 7A) (see also Martini and Schachner, 1986, and references therein). As with PMP22, significant levels of MAG (Fig.…”

Role of Src Kinases in the ADAM-mediated Release of L1 Adhesion Molecule from Human Tumor Cells

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