Noncoordinate regulation of myelinogenic parameters in primary cultures of dissociated fetal rat brain.

The developmental regulation of sulfogalactosylceramide (sulfatide) synthesis, 2', 3'-cyclic nucleotide-3'-phosphohydrolase activity (CNP), and myelin basic protein (MBP) accumulation, three markers characteristic of myelinogenesis, were observed in dispersed cultures of fetal rat brain in spite of the absence of the formation of compact, multilamellar myelin. Sulfatide synthetic rate and CNP activity began to increase by 8 days in vitro (DIV) (approximately comparable to days post-natal) and reached their maxima by 20 DIV. MBP began to accumulate after 14 DEV and reached a maximum by 38 DIV. Thus, the temporal regulation of the onset of expression of these parameters, which is coordinate in vivo, has been dissociated into two sequential periods in vitro. Similarly, the regulatory mechanisms controlling the subsequent decline of the net expression of these three parameters were dissociated. Whereas, the increase in the net CNP activity ceased on schedule, the decline of sulfatide synthetic rate was delayed 20 days, and the accumulation of MBP underwent a net loss. These data suggest that there are multiple parallel but separate mechanisms of temporal regulation controlling myelinogenic gene expression, and that, among them, those factors that control MBP accumulation are more sensitive to disruption by the rigors of dissociated culture.