A CNS-SPECIFIC POU TRANSCRIPTION FACTOR, BRN-2, IS REQUIRED FOR ESTABLISHING MAMMALIAN NEURAL CELL LINEAGES

The pluripotent embryonal carcinoma cell line P19 can differentiate in vitro into neurons and astrocytes. By employing this neural cell diff erentiation system, we have studied the expression and function of a P OU transcription factor implicated in mammalian neurogenesis. When P19 cells differentiated to the neural cells, one of the CNS-specific POU genes (Brn-2) was selectively induced. The induction of Brn-2 was spe cific to the neural cell lineages and took place at the early stage of differentiation. When the Brn-2 induction was blocked/delayed by anti sense RNA, such cells were unable to differentiate to neurons and astr ocytes. Instead they differentiated to nonneural cells, including smoo th and skeletal muscle cells. Furthermore, with reduced levels of anti sense RNA, differentiation to neural cells occurred. These results ind icate that Brn-2 is essential for the neural cell differentiation of P 19 cells and suggest that Brn-2 is one of the genes required for estab lishing neural cell lineages in mammals.