DISTRIBUTION OF THE PHOSPHORYLATED MICROTUBULE-ASSOCIATED PROTEIN-TAUIN DEVELOPING CORTICAL-NEURONS

During brain development, the microtubule-associated protein tau prese nts a transient state of high phosphorylation. We have investigated th e developmental distribution of the phosphorylated fetal-type tau in t he developing rat cortex and in cultures of embryonic cortical neurons , using antibodies which react with tau in a phosphorylation-dependent manner. The phosphorylated fetal-type tau was present in the developi ng cortex at 20 days but not at 18 days of embryonic life and was not detected before four to five days in neuronal culture. The cyclin-depe ndent kinase p34(cdc2) was expressed only in germinal layers in the em bryonic brain and was not co-localized with phosphorylated tau. After 10 days of postnatal life, the phosphorylated tau progressively disapp eared from cortical neurons, disappearing first from the deepest corti cal layers where neurons are ontogenetically the oldest. Phosphorylate d tau was found in axons and dendrites of cortical neurons at all deve lopmental stages whereas unphosphorylated tau tended to disappear from dendrites during development. The timing of appearance of phosphoryla ted tau in the cortex, by comparison with the expression of other deve lopmental markers, indicates that phosphorylated tau is present at a h igh level only during the period of intense neuritic outgrowth and tha t it disappears during the period of neurite stabilization and synapto genesis, concomitantly to the expression of adult tau isoforms. In con trol cultures and in cultures treated with colchicine, the phosphoryla ted tau was not associated to cold-stable and to colchicine-resistant microtubules. These in vivo results suggest that the high expression o f phosphorylated tau species is correlated with the presence of a dyna mic microtubule network during a period of high plasticity in the deve loping brain.