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 m orphogenesis, neurofibrillary tangle formation and neurodegeneration h ave not been completely clarified. We found that the expression of tau proteins in primary cultures of cerebellar granule cells from neonata l rat brain is a developmentally regulated process affecting tau synth esis at different levels. Changes in tan RNA splicing are clearly demo nstrated by PCR data showing the switching on of the mRNA containing f our internal repeats by DIV 6 and the switching off of the mRNA contai ning three internal repeats after DIV 12. The changes in mRNA levels o f the different tau isoforms during development in vitro occur in para llel with changes in tau protein expression, both qualitatively and qu antitatively, as shown by Western analysis of protein extracts from gr anule cells at different DIV with an anti-tau polyclonal antibody. Fin ally, as indicated by MAP2 and tau immunocytochemistry data, the switc h in tau protein expression appears to be contemporary with neurite ou tgrowth and cell differentiation. Our data suggest that a differential expression of various tau proteins parallels the degree of cell matur ation.