Caviness V S, Goto T, Tarui T, Takahashi T, Bhide P G, Nowakowski R S
Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Cereb Cortex. 2003 Jun;13(6):592-8. doi: 10.1093/cercor/13.6.592.
The neurons of the neocortex are generated over a 6 day neuronogenetic interval that comprises 11 cell cycles. During these 11 cell cycles, the length of cell cycle increases and the proportion of cells that exits (Q) versus re-enters (P) the cell cycle changes systematically. At the same time, the fate of the neurons produced at each of the 11 cell cycles appears to be specified at least in terms of their laminar destination. As a first step towards determining the causal interrelationships of the proliferative process with the process of laminar specification, we present a two-pronged approach. This consists of (i) a mathematical model that integrates the output of the proliferative process with the laminar fate of the output and predicts the effects of induced changes in Q and P during the neuronogenetic interval on the developing and mature cortex and (ii) an experimental system that allows the manipulation of Q and P in vivo. Here we show that the predictions of the model and the results of the experiments agree. The results indicate that events affecting the output of the proliferative population affect both the number of neurons produced and their specification with regard to their laminar fate.
新皮层的神经元在一个包含11个细胞周期的6天神经发生间隔内产生。在这11个细胞周期中，细胞周期的长度增加，退出（Q）与重新进入（P）细胞周期的细胞比例发生系统性变化。与此同时，在11个细胞周期的每个周期产生的神经元命运似乎至少在其层状定位方面已被确定。作为确定增殖过程与层状定位过程之间因果关系的第一步，我们提出了一种双管齐下的方法。这包括：（i）一个数学模型，该模型将增殖过程的输出与输出的层状命运整合在一起，并预测在神经发生间隔期间Q和P的诱导变化对发育中和成熟皮层的影响；（ii）一个允许在体内操纵Q和P的实验系统。在这里，我们表明模型的预测与实验结果一致。结果表明，影响增殖群体输出的事件会影响产生的神经元数量及其在层状命运方面的定位。
