Cai Li, Hayes Nancy L, Takahashi Takao, Caviness Verne S, Nowakowski Richard S
Department of Neuroscience and Cell Biology, UMDNJ-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.
J Neurosci Res. 2002 Sep 15;69(6):731-44. doi: 10.1002/jnr.10398.
Mechanisms that regulate neuron production in the developing mouse neocortex were examined by using a retroviral lineage marking method to determine the sizes of the lineages remaining in the proliferating population of the ventricular zone during the period of neuron production. The distribution of clade sizes obtained experimentally in four different injection-survival paradigms (E11-E13, E11-E14, E11-E15, and E12-E15) from a total of over 500 labeled lineages was compared with that obtained from three models in which the average behavior of the proliferating population [i.e., the proportion of cells remaining in the proliferative population (P) vs. that exiting the proliferative population (Q)] was quantitatively related to lineage size distribution. In model 1, different proportions of asymmetric, symmetric terminal, and symmetric nonterminal cell divisions coexisted during the entire developmental period. In model 2, the developmental period was divided into two epochs: During the first, asymmetric and symmetric nonterminal cell divisions occurred, but, during the second, asymmetric and symmetric terminal cell divisions occurred. In model 3, the shifts in P and Q are accounted for by changes in the proportions of the two types of symmetric cell divisions without the inclusion of any asymmetric cell divisions. The results obtained from the retroviral experiments were well accounted for by model 1 but not by model 2 or 3. These findings demonstrate that: 1) asymmetric and both types of symmetric cell divisions coexist during the entire period of neurogenesis in the mouse, 2) neuron production is regulated in the proliferative population by the independent decisions of the two daughter cells to reenter S phase, and 3) neurons are produced by both asymmetric and symmetric terminal cell divisions. In addition, the findings mean that cell death and/or tangential movements of cells in the proliferative population occur at only a low rate and that there are no proliferating lineages "reserved" to make particular laminae or cell types.
通过使用逆转录病毒谱系标记方法，研究了发育中的小鼠新皮质中调节神经元产生的机制，以确定在神经元产生期间，脑室区增殖群体中剩余谱系的大小。将在四种不同注射-存活范式（E11-E13、E11-E14、E11-E15和E12-E15）中通过实验获得的、来自总共500多个标记谱系的进化枝大小分布，与从三个模型中获得的分布进行比较，在这三个模型中，增殖群体的平均行为[即留在增殖群体中的细胞比例（P）与离开增殖群体的细胞比例（Q）]与谱系大小分布存在定量关系。在模型1中，在整个发育时期，不同比例的不对称、对称终末和对称非终末细胞分裂共存。在模型2中，发育时期分为两个阶段：在第一个阶段，发生不对称和对称非终末细胞分裂，但在第二个阶段，发生不对称和对称终末细胞分裂。在模型三3中，P和Q的变化是由两种对称细胞分裂比例的变化引起的，其中不包括任何不对称细胞分裂。逆转录病毒实验得到的结果可以很好地由模型1解释，但不能由模型2或模型3解释。这些发现表明：1）在小鼠神经发生的整个时期，不对称和两种类型的对称细胞分裂共存；2）在增殖群体中，神经元的产生是由两个子细胞重新进入S期的独立决定所调节的；3）神经元是由不对称和对称终末细胞分裂产生的。此外，这些发现意味着增殖群体中的细胞死亡和/或细胞的切向运动发生率很低，并且不存在为形成特定层或细胞类型而“保留”的增殖谱系。
