Size distribution of retrovirally marked lineages matches prediction from population measurements of cell cycle behavior
Size distribution of retrovirally marked lineages matches prediction from population measurements of cell cycle behavior
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DOI：
10.1002/jnr.10398
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发表时间：
2002-09-15
影响因子：
4.2
通讯作者：
Nowakowski, RS
中科院分区：
文献类型：
--
作者：
Cai, L;Hayes, NL;Nowakowski, RS
通过使用逆转录病毒谱系标记方法来检查调节发育中小鼠新皮层中神经元产生的机制，以确定神经元产生期间心室区增殖群体中剩余的谱系的大小。将从总共超过500个标记的谱系中在四种不同的注射-存活范例（E11-E13、E11-E14、E11-E15和E12-E15）中实验获得的进化枝大小的分布与从三种模型中获得的进化枝大小的分布进行比较，在三种模型中增殖群体的平均行为[即，保留在增殖群体中的细胞比例（P）与退出增殖群体的细胞比例（Q）]与谱系大小分布定量相关。在模型1中，不同比例的不对称，对称的终端，和对称的非终端细胞分裂在整个发育期间共存。在模型2中，发育期分为两个时期：在第一，不对称和对称的非终末细胞分裂发生，但在第二，不对称和对称的终末细胞分裂发生。在模型3中，P和Q的变化是由两种类型的对称细胞分裂的比例变化引起的，而不包括任何不对称细胞分裂。模型1很好地解释了从逆转录病毒实验中获得的结果，但模型2或3没有解释。这些研究结果表明：1）在小鼠神经元发生的整个期间，不对称和两种类型的对称细胞分裂共存，2）在增殖群体中，神经元的产生由两个子细胞重新进入S期的独立决定调节，以及3）神经元由不对称和对称终末细胞分裂产生。此外，这些发现意味着增殖群体中的细胞死亡和/或细胞的切向运动仅以低速率发生，并且没有增殖谱系“保留”以形成特定的层或细胞类型。(C)2002 Wiley-Liss，Inc.
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 neuronogenesis 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. (C) 2002 Wiley-Liss, Inc.