Species-specific segmentation clock periods are due to differential biochemical reaction speeds
Species-specific segmentation clock periods are due to differential biochemical reaction speeds
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DOI：
10.1126/science.aba7668
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发表时间：
2020-09-18
期刊：
影响因子：
56.9
通讯作者：
Ebisuya, Miki
中科院分区：
文献类型：
--
作者：
Matsuda, Mitsuhiro;Hayashi, Hanako;Ebisuya, Miki
虽然小鼠和人类的胚胎发育机制相似，但人类的时间尺度通常较慢。为了研究这些种间差异的发展，我们概括小鼠和人类的分段时钟显示2- 3小时和5- 6小时的振荡周期，分别。我们的种间基因组交换分析表明，周期差异不是由于HES 7位点的序列差异，分割时钟的核心基因。相反，我们证明了HES 7的多种生化反应，包括降解和表达延迟，在人类细胞中比在小鼠细胞中慢。通过测量的生化参数，我们的数学模型解释了物种之间两到三倍的周期差异。我们建议，细胞自主的生化反应速度的差异的基础上的物种之间的发展的时间差异。
Although mechanisms of embryonic development are similar between mice and humans, the time scale is generally slower in humans. To investigate these interspecies differences in development, we recapitulate murine and human segmentation clocks that display 2- to 3-hour and 5- to 6-hour oscillation periods, respectively. Our interspecies genome-swapping analyses indicate that the period difference is not due to sequence differences in the HES7 locus, the core gene of the segmentation clock. Instead, we demonstrate that multiple biochemical reactions of HES7, including the degradation and expression delays, are slower in human cells than they are in mouse cells. With the measured biochemical parameters, our mathematical model accounts for the two- to threefold period difference between the species. We propose that cell-autonomous differences in biochemical reaction speeds underlie temporal differences in development between species.