Developmental regulation of alternatively spliced isoforms of mRNA encoding MAP2 and tau in rat brain oligodendrocytes during culture maturation.

Oligodendrocytes are responsible for the formation and maintenance of the myelin sheaths in the central nervous system (CNS), and microtubules essentially participate in the elaboration and stabilization of myelin-containing cellular processes. We have shown before that the two major groups of neuronal microtubule-associated proteins (MAPs), MAP2 and tau, are expressed in the myelin forming cells of the CNS (Mueller et al. [1997] Cell Tissue Res. 288:239-249). Here we demonstrate for the first time that during culture maturation, changes in mRNA splicing and a shift from immature to mature MAP2 and tau mRNAs occur in oligodendrocytes. Similarly to neurons, a developmental shift from MAP2 isoforms with 3 microtubule (MT)-binding domains (3R) to the isoforms with 4 MT-binding domains (4R) is observable. MAP2c constitutes the major MAP2 isoform in oligodendrocytes. They contain tau mRNA splice products with both 3 and 4 MT-binding repeats (3R, 4R) with no amino terminal insert or with exon 2, and do not express isoforms containing exon 3. The shortest form tau 1 (3R; no inserts) representing the immature tau isoform is most prominently expressed in early progenitor cells and gradually decreases during culture maturation, while tau 5 (4R; with exon 2) appears later during in vitro differentiation. The product corresponding to tau 2 (3R; with exon 2) and tau 4 (4R; no inserts) remains approximately at the same level. Hence, the occurrence of MAPs in oligodendrocytes is developmentally regulated. While in progenitor cells, 3R- and 4R-MAP2c are expressed at approximately the same level, in mature oligodendrocytes after 12 days in vitro, the ratio of 4R- to 3R-MAP2c is nearly 2. In contrast, the ratio of 4R- to 3R-tau in progenitor cells is 1:3 and shifts to 1:1 after 12 days in culture.