REGULATION OF OLIGODENDROCYTE DIFFERENTIATION - PROTEIN-KINASE-C ACTIVATION PREVENTS DIFFERENTIATION OF O2A PROGENITOR CELLS TOWARD OLIGODENDROCYTES

Oligodendrocytes differentiate on a specific schedule in vivo in order to myelinate axons at the precise time and at the appropriate positio n. The current study was undertaken to obtain further insight as to ho w this timed appearance is regulated intracellularly. We observed that exposure of O2A progenitor cells in culture to phorbol 12-myristate 1 3-acetate (PMA; an activator of protein kinase C, PKC) inhibited their differentiation to oligodendrocytes by suppressing the expression of specific myelin markers at the O4-stage. To positively identify a role of PKC per se in differentiation, the use of a minimal medium with lo w serum content turned out to be essential. This was demonstrated by s howing that the inhibitory effect of PMA on oligodendrocyte differenti ation could be completely abolished by a combined action of insulin, t riiodothyronine (T3), hydrocortisone and other components of a chemica lly defined medium (CDM). Furthermore, the PMA-mediated inhibition of oligodendrocyte differentiation could be partially restored by activat ion of the cAMP signal transduction pathway. The results indicate that PKC plays a crucial role in the differentiation of O2A progenitor cel ls toward oligodendrocytes: PKC activation prevents differentiation of O2A progenitor cells, whereas differentiation toward oligodendrocytes is dependent on other signaling compounds which may counteract the PK C signal transduction route. (C) 1998 Wiley-Liss, Inc.