Mammalian embryos show metabolic plasticity toward the surrounding environment during neural tube closure.
Mammalian embryos show metabolic plasticity toward the surrounding environment during neural tube closure.
复制标题
哺乳动物胚胎在神经管闭合过程中表现出对周围环境的代谢可塑性。
DOI：
10.1111/gtc.12626
复制
发表时间：
2018
期刊：
影响因子：
2.1
通讯作者：
Miura M.
中科院分区：
文献类型：
--
作者：
Miyazawa H;Yamamoto M;Yamaguchi Y;Miura M.
发育中的胚胎会重新连接发育过程的能量代谢。然而，人们对代谢重连如何以时空方式与发育相结合知之甚少。在这里，我们发现哺乳动物胚胎在神经管闭合（NTC）阶段表现出葡萄糖代谢的可塑性，以响应细胞外环境，此时宫内环境在胎盘形成时发生变化。为了研究胚胎如何根据环境变化调节其代谢状态，我们使用酶测定和基因编码的 ATP 传感器分析了暴露于宫外环境时 ATP 的稳态水平。当环境发生变化时，NTC 阶段的胚胎表现出 ATP 含量增加，而 NTC 之前和之后的胚胎则没有。 NTC 阶段胚胎中 ATP 的增加似乎取决于糖酵解。有趣的是，在神经外胚层（NE）和非神经外胚层（NNE）区域的神经板边缘也观察到线粒体膜电位（ΔΨm）增加。这意味着糖酵解可以与 NE 和神经板边界中的 TCA 循环结合，具体取决于环境背景。破坏 ΔΨm 会抑制颅神经板的折叠。因此，我们建议胚胎调节代谢可塑性，以实现 NTC 阶段葡萄糖代谢与细胞外环境的耦合。
Developing embryos rewire energy metabolism for developmental processes. However, little is known about how metabolic rewiring is coupled with development in a spatiotemporal manner. Here, we show that mammalian embryos display plasticity of glucose metabolism in response to the extracellular environment at the neural tube closure (NTC) stage, when the intrauterine environment changes upon placentation. To study how embryos modulate their metabolic state upon environmental change, we analyzed the steady‐state level of ATP upon exposure to extrauterine environments using both an enzymatic assay and a genetically encoded ATP sensor. Upon environmental changes, NTC‐stage embryos exhibited increased ATP content, whereas embryos before and after NTC did not. The increased ATP in the NTC‐stage embryos seemed to depend on glycolysis. Intriguingly, an increase in mitochondrial membrane potential (ΔΨm) was also observed in the neural ectoderm (NE) and the neural plate border of the non‐neural ectoderm (NNE) region. This implies that glycolysis can be coupled with the TCA cycle in the NE and the neural plate border depending on environmental context. Disrupting ΔΨm inhibited folding of the cranial neural plate. Thus, we propose that embryos tune metabolic plasticity to enable coupling of glucose metabolism with the extracellular environment at the NTC stage.