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 m yelin sheaths in the central nervous system (CNS), and microtubules essenti ally participate in the elaboration and stabilization of myelin-containing cellular processes. We have shown before that the two major groups of neuro nal 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 m aturation, changes in mRNA splicing and a shift from immature to mature MAP 2 and tau mRNAs occur in oligodendrocytes. Similarly to neurons, a developm ental shift from MAP2 isoforms with 3 microtubule (MT)-binding domains (3R) to the isoforms with 4 MT-binding domains (4R) is observable. MAP2c consti tutes the major MAP2 isoform in oligodendrocytes. They contain tau mRNA spl ice products with both 3 and 4 MT-binding repeats (3R, 4R) with no amino te rminal 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 is oform 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 s ame level. Hence, the occurrence of MAPs in oligodendrocytes is development ally regulated. While in progenitor cells, 3R- and 4R-MAP2c are expressed a t 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 i n culture. J. Neurosci. Res. 56:259-270, 1999. (C) 1999 Wiley-Liss, Inc.