The Phox2b transcription factor coordinately regulates neuronal cell cycleexit and identity

In the vertebrate neural tube, cell cycle exit of neuronal progenitors is a ccompanied by the expression of transcription factors that define their gen eric and sub-type specific properties, but how the regulation of cell cycle withdrawal intersects with that of cell fate determination is poorly under stood. Here we show by both loss- and gain-of-function experiments that the neuronal-subtype-specific homeodomain transcription factor Phox2b drives p rogenitor cells to become post-mitotic, In the absence of Phox2b, post-mito tic neuronal precursors are not generated in proper numbers. Conversely, fo rced expression of Phox2b in the embryonic chick spinal cord drives ventric ular zone progenitors to become post-mitotic neurons and to relocate to the mantle layer. In the neurons thus generated, ectopic expression of Phox2b is sufficient to initiate a programme of motor neuronal differentiation cha racterised by expression of Islet1 and of the cholinergic transmitter pheno type, in line with our previous results showing that Phox2b is an essential determinant of cranial motor neurons, These results suggest that Phox2b co ordinates quantitative and qualitative aspects of neurogenesis, thus ensuri ng that neurons of the correct phenotype are generated in proper numbers at the appropriate times and locations.