RIKEN Center for Biosystems Dynamics Research (RIKEN BDR), 2-2-3 Minatojima-minamimachi, Chuo-ku, 650-0047 Kobe, Japan.
European Molecular Biology Laboratory (EMBL) Barcelona, Dr. Aiguader 88, 08003 Barcelona, Spain.
Science. 2020 Sep 18;369(6510):1450-1455. doi: 10.1126/science.aba7668.
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 locus, the core gene of the segmentation clock. Instead, we demonstrate that multiple biochemical reactions of , 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.
尽管小鼠和人类胚胎发育的机制相似，但时间尺度在人类中通常较慢。为了研究这些物种间发育的差异，我们重现了分别显示 2-3 小时和 5-6 小时振荡周期的鼠类和人类体节时钟。我们的种间基因组交换分析表明，周期差异不是由于 基因座的序列差异引起的，该基因座是体节时钟的核心基因。相反，我们证明了 的多个生化反应，包括降解和表达延迟，在人类细胞中比在小鼠细胞中更慢。利用测量的生化参数，我们的数学模型解释了两个物种之间两到三倍的周期差异。我们提出，生化反应速度的细胞自主性差异是物种间发育时间差异的基础。
