CELL PROLIFERATION IN DEVELOPING HIPPOCAMPAL REGION

发育中海马区的细胞增殖

• 批准号: 3414510
• 负责人: Richard S Nowakowski
• 金额: $ 10.91万
• 依托单位: UNIV OF MED/DENT NJ-R W JOHNSON MED SCH
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-07-01 至 1995-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3414510
• 关键词: DNA replication; Retroviridae; Retroviridae disease; autoradiography; cell cycle; cell growth regulation; cell migration; cytogenetics; dentate gyrus; genetic models; glia; immunocytochemistry; laboratory mouse; mathematics; model design /development; neurogenesis; neurons; tritium

The regulation of cell number and, more specifically, neuron number in the developing CNS is a largely unexplored question. Any answer to this question must consider two important developmental issues: 1) the regulation of neuronal production and 2) the phenomenon of naturally occurring cell death. This project is concerned with the first of these issues. We will determine: 1) how the relative number of proliferative cells changes during the development of a structure, 2) how frequently the proliferative cells divide, and 3) what proportion of the proliferative population becomes permanently post-mitotic at each pass through the cell cycle. We will examine this issue in four different proliferative zones in the developing hippocampal region of the mouse: 1) the ventricular zone of the hippocampus and subiculum, 2) the ventricular zone of the periallocortex (presubiculum, parasubiculum and entorhinal area, 3) the subventricular zone of the periallocortex, and 4) the intrahilar proliferative zone of the dentate gyrus. We will measure the length of the cell cycle (Tc) and the DNA-synthetic phase (Ts) for all of the proliferative population and also for that subpopulation which will produce neurons. For several ages, the proportion of the daughter cells that leave the proliferative zones to become permanently post-mitotic will be determined to test the hypothesis that during developing that proportion increases gradually such that the proliferative population becomes self-exhausting several generations before cell proliferation for that structure ceases. The output of the proliferative zones will be measured by determining the distribution of cells that leave each of the four proliferative populations within a one-hour period (i.e., a "one-hour cohort"). The pattern of distribution of labeled cells from retroviral infections for progeny from three of the four different proliferative populations will be determined. We will develop three probabilistically- driven cytogenetic and histogenic models, a cytokinetic model, and output (or cell proliferation) model, and a cell dispersion model. The model will be used to determine if the results of the various experiments are consistent internally and with each other and to make specific testable predictions. The major methods to be used are: 1) bromodeoxyuridine immunohistochemistry and tritiated thymidine autoradiography both alone and in a series of double labeling experiments, and 2) retroviral transfection of clonally related populations.

细胞数量的调节，更具体地说，神经元数量的调节， 开发CNS是一个很大程度上未探索的问题。 有什么答案吗 问题必须考虑两个重要的发展问题：（1） 调节神经元的生产和2）自然现象， 发生细胞死亡。 本项目涉及其中的第一个 问题. 我们将确定：1）如何相对数量的增殖 细胞在结构发育过程中发生变化，2） 增殖细胞分裂，3）增殖细胞的比例是多少？ 在每次通过细胞时，细胞群变成永久性的有丝分裂后 周期 我们将在四个不同的增殖区研究这个问题 在发育中的小鼠海马区：1）心室 海马和下托区，2）脑室区， 皮质周围区（下托前区、下托旁区和内嗅区）; 4）肺门内 齿状回的增殖区。 我们将测量 细胞周期（Tc）和DNA合成期（Ts）的所有的 增殖群体以及将 产生神经元。 在几个年龄段，子细胞的比例 使增殖区永久性地成为有丝分裂后的意志 决心测试假设，在开发过程中， 比例逐渐增加， 在细胞增殖之前的几代人中， 这种结构停止了。 增殖区的输出将是 通过确定离开每个细胞的细胞分布来测量， 一小时内的四个增殖群体（即，一小时 队列"）。 逆转录病毒标记细胞的分布模式 四种不同的增殖性病毒中的三种的后代的感染 人口将被确定。 我们将从概率上发展出三个- 驱动的细胞遗传学和组织遗传学模型，细胞动力学模型，和输出 (or细胞增殖）模型和细胞分散模型。 模型 将用于确定各种实验的结果是否 内部一致，相互一致，并使特定的可测试性 预测。 主要方法有：1）溴脱氧尿苷 免疫组织化学和氚标记胸苷放射自显影 在一系列的双标记实验中，以及2）逆转录病毒 克隆相关群体的转染。