Differential expression of fetal and mature tau isoforms in primary cultures of rat cerebellar granule cells during differentiation in vitro.

The molecular mechanism(s) responsible for the differential expression of various tau protein isoforms as well as their functional role in morphogenesis, neurofibrillary tangle formation and neurodegeneration have not been completely clarified. We found that the expression of tau proteins in primary cultures of cerebellar granule cells from neonatal rat brain is a developmentally regulated process affecting tau synthesis at different levels. Changes in tau RNA splicing are clearly demonstrated by PCR data showing the switching on of the mRNA containing four internal repeats by DIV 6 and the switching off of the mRNA containing three internal repeats after DIV 12. The changes in mRNA levels of the different tau isoforms during development in vitro occur in parallel with changes in tau protein expression, both qualitatively and quantitatively, as shown by Western analysis of protein extracts from granule cells at different DIV with an anti-tau polyclonal antibody. Finally, as indicated by MAP2 and tau immunocytochemistry data, the switch in tau protein expression appears to be contemporary with neurite outgrowth and cell differentiation. Our data suggest that a differential expression of various tau proteins parallels the degree of cell maturation.