Expression of the antiproliferative gene TIS21 at the onset of neurogenesis identifies single neuroepithelial cells that switch from proliferative toneuron-generating division

At the onset of mammalian neurogenesis, neuroepithelial (NE) cells switch f rom proliferative to neuron-generating divisions, Understanding the molecul ar basis of this switch requires the ability to distinguish between these t wo types of division. Here we show that in the mouse ventricular zone, expr ession of the mRNA of the antiproliferative gene TIS21 (PC3, BTG2) (i) star ts at the onset of neurogenesis, (ii) is confined to a subpopulation of NE cells that increases in correlation with the progression of neurogenesis, a nd (iii) is not detected in newborn neurons. Expression of the TIS21 mRNA i n the NE cells occurs transiently during the cell cycle, i.e., in the G(1) phase. In contrast to the TIS21 mRNA, the TIS21 protein persists through th e division of NE cells and is inherited by the neurons, where it remains de tectable during neuronal migration and the initial phase of differentiation . Our observations indicate that the TIS21 gene is specifically expressed i n those NE cells that, at their next division, will generate postmitotic ne urons, but not in proliferating NE cells. Using TIS21 as a marker, we find that the switch from proliferative to neuron-generating divisions is initia ted in single NE cells rather than in synchronized neighboring cells.