Computational models of neocortical neuronogenesis and programmed cell death in the developing mouse, monkey, and human
Computational models of neocortical neuronogenesis and programmed cell death in the developing mouse, monkey, and human
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DOI：
10.1093/cercor/bhl151
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发表时间：
2007-10-01
期刊：
影响因子：
3.7
通讯作者：
Faustman, Elaine M.
中科院分区：
文献类型：
--
作者：
Gohlke, Julia M.;Griffith, Wifliani C.;Faustman, Elaine M.
本文提出了一种计算模型，可以定量模拟跨哺乳动物物种新皮质神经元数量的获取。当将啮齿类动物的科学发现推断到人类时，特别需要承认人类进化过程中新皮质加速扩大的重要性。新皮质发育的特点是神经祖细胞增殖和死亡、神经元分化和神经元程序性细胞死亡的离散阶段。我们基于实验得出的细胞周期长度、细胞周期退出和细胞死亡参数，开发了人类和恒河猴新皮质神经元细胞获取的计算模型。我们的模型结果与估计成年和发育中的恒河猴和人类新皮质神经元数量的独立体视学研究一致。我们的灵长类动物模型与先前开发的啮齿动物模型的比较表明，神经元发生期持续时间的延长与细胞周期进展和死亡的细胞过程的延长之间的相关性可以解释灵长类新皮质大小的巨大增加。此外，与啮齿类动物相比，我们预测细胞死亡可能在灵长类新皮质的塑造中发挥更大的作用。我们的新皮质发育和进化的数学模型为啮齿动物和人类之间的外推提供了基于生物学的定量结构。这些模型可以帮助将未来的实验研究集中在啮齿动物与人类新皮质发育的不同机制上。
This paper presents a computational model allowing quantitative simulations of acquisition of neocortical neuronal number across mammalian species. When extrapolating scientific findings from rodents to humans, it is particularly pertinent to acknowledge the importance of the accelerated enlargement of the neocortex during human evolution. Neocortex development is marked by discrete stages of neural progenitor cell proliferation and death, neuronal differentiation, and neuronal programmed cell death. We have developed computational models of human and rhesus monkey neocortical neuronal cell acquisition based on experimentally derived parameters of cell cycle length, commitment to cell cycle exit, and cell death. Our model results agree with independent stereological studies estimating neocortical neuron number in adult and developing rhesus monkey and human. Comparisons of our primate models with previously developed rodent models suggest correlations between the lengthening of the duration of the neuronogenesis period and a lengthening of the cellular processes of cell cycle progression and death can account for the vast increase in size of the primate neocortex. Furthermore, when compared with rodents, we predict that cell death may play a larger role in shaping the primate neocortex. Our mathematical models of the development and evolution of the neocortex provide a quantitative, biologically based construct for extrapolation between rodent and humans. These models can assist in focusing future experimental research on the differing mechanisms of rodent versus human neocortical development.