A Cellular and Molecular Approach to Myelinogenesis in the CNS of Trout

Abstract

Myelin is an extension of the glial plasmamembrane that surrounds axons as a multilamellar insulating sheath to permit a most efficient and fast mode of signal propagation, the saltatory impulse conduction (Raine, 1984; Ritchie, 1984). Two distinct types of glial cells are responsible for the elaboration of myelin in central and peripheral nerve fibers, respectively, which basically differ from each other in terms of cell structure, molecular phenotype, and cell lineage relationship. Oligodendrocytes, the myelin-forming cells in the central nervous system (CNS) each elaborate numerous slender processes to ensheath a multitude of internodes on different axons (Sternberger et al., 1978; Wood and Bunge, 1984; Pfeiffer et al., 1993). Schwann cells, which produce myelin in the peripheral nervous system (PNS) on the other hand, are always closely associated with an individual nerve fiber and strictly establish a one-to-one relationship with a single internodal segment (Peters et al., 1976; Rumsby and Crang, 1977); Furthermore, these cells typically are surrounded by a basal lamina produced by themselves, which is critically involved in the initiation of the myelination process in the PNS (Bunge et al., 1986). This diversity in cellular morphology further extends into characteristic differences in the biochemical features of the myelin synthesized by either cell type (Fig. 1). Myelin generated in the CNS by oligodendrocytes is characterized by a high proportion of a strongly hydrophobic, nonglycosylated proteolipidprotein (PLP) (Lees and Brostoff, 1984), which comprises four transmembrane segments and is thought to accomplish the tight apposition of external glial membrane faces (Laursen et al., 1984; Stoffel et al., 1984) at the ultrastructural level giving rise to the intraperiod line (Braun, 1984). The major gene product of Schwann cells by contrast is a hydrophobic glycoprotein of about 29 kDa mol wt, possessing only a single membrane spanning domain, which is called P_o (Everly et al., 1973; Lemke and Axel, 1985). The extracellular domain of this protein exhibits an immunoglobulin-like secondary structure enabling it to convey external adhesion of the glial lamellae by homophilic molecular interactions (Lemke, 1988; Filbin et al., 1990; D’Urso et al., 1990). The cytoplasmic portion of the molecule is highly basic and is thought to align with polar headgroups of membrane lipids, thus helping to stick together adjacent cytoplasmic membrane faces (Lemke and Axel, 1985). Although PLP and P_o seem to functionally replace each other in CNS and PNS myelin, respectively, they do not exhibit any appreciable sequence homologies and are entirely different with respect to their membrane topology and genomic arrangements (Laursen et al., 1984; Stoffel et al., 1984; Lemke et al., 1988; Nave and Milner, 1989). A major structural constituent shared by both types of myelin is myelin-basic protein (Carnegie and Dunkley, 1975; Roach et al., 1983), a hydrophilic component of about 18 kDa with an isoelectric point of about 10, which occurs in a number of alternative splice variants in the CNS (deFerra et al., 1985). All of them are extrinsic myelin components synthesized on free polyribosomes (Colman et al.,1982), their mRNAs being transported out into the cellular periphery along cytoskeletal tracts (Brophy et al., 1993). The translated proteins are attached to the cytoplasmic surface of the glial extensions to fuse myelin at the major dense line (Privat et al., 1987; Omlin et al., 1988). Compact myelin as described above is a feature unique to the vertebrate nervous tissue that is initially encountered in the phylogenetically ancient classes of fish (bony and cartilaginous fishes), whereas it does not occur in invertebrates (see also previous chapter).