Remodeling of the metabolome during early frog development.
Remodeling of the metabolome during early frog development.
复制标题
DOI：
10.1371/journal.pone.0016881
复制
发表时间：
2011-02-04
期刊：
影响因子：
3.7
通讯作者：
Kirschner MW
中科院分区：
文献类型：
--
作者：
Vastag L;Jorgensen P;Peshkin L;Wei R;Rabinowitz JD;Kirschner MW
在许多动物物种中，包括非洲爪蟾（Xenopus laevis）在内，一系列快速的同步细胞分裂启动了胚胎发生。在许多这些分裂周期之后，核质比增加到足以以某种方式导致细胞周期延长并在中期囊胚转变（MBT）时变得不同步。我们已经发现，一个意想不到的核心代谢途径的重塑发生在卵裂周期和MBT在X.laevis，代谢物丰度的广泛变化证明。虽然一直观察到代谢物丰度的许多变化，但也很明显，不同的雌性青蛙产卵时至少有一些代谢物的水平不同。用重同位素追踪代谢物表明，丙氨酸被消耗以产生早期胚胎的能量。发现dATP池在MBT期间下降，并且我们已经证实，在MBT开始时，母体dNTP池在功能上耗尽。我们的研究结果支持另一种假设，即在MBT的细胞周期延长是由一个有限的母体蛋白质，通常提出的，而是由DNA合成的需求呈指数增长所带来的dNTP池下降。
A rapid series of synchronous cell divisions initiates embryogenesis in many animal species, including the frog Xenopus laevis. After many of these cleavage cycles, the nuclear to cytoplasmic ratio increases sufficiently to somehow cause cell cycles to elongate and become asynchronous at the mid-blastula transition (MBT). We have discovered that an unanticipated remodeling of core metabolic pathways occurs during the cleavage cycles and the MBT in X.laevis, as evidenced by widespread changes in metabolite abundance. While many of the changes in metabolite abundance were consistently observed, it was also evident that different female frogs laid eggs with different levels of at least some metabolites. Metabolite tracing with heavy isotopes demonstrated that alanine is consumed to generate energy for the early embryo. dATP pools were found to decline during the MBT and we have confirmed that maternal pools of dNTPs are functionally exhausted at the onset of the MBT. Our results support an alternative hypothesis that the cell cycle lengthening at the MBT is triggered not by a limiting maternal protein, as is usually proposed, but by a decline in dNTP pools brought about by the exponentially increasing demands of DNA synthesis.