Sakai Daisuke, Murakami Yuki, Shigeta Daichi, Tomosugi Mitsuhiro, Sakata-Haga Hiromi, Hatta Toshihisa, Shoji Hiroki
Department of Biology, Kanazawa Medical University, Uchinada, Ishikawa, Japan.
Department of Hygiene and Public Health, Kansai Medical University, Osaka, Japan.
Front Cell Dev Biol. 2023 Jul 3;11:1212375. doi: 10.3389/fcell.2023.1212375. eCollection 2023.
Physiological hypoxia is critical for placental mammalian development. However, the underlying mechanisms by which hypoxia regulates embryonic development remain unclear. We discovered that the expression of glycolytic genes partially depends on hypoxia in neuroepithelial cells of E8.25 mouse embryos. Consistent with this finding, inhibiting glycolysis during the early phase of neural tube closure (E8.0-8.5) resulted in a neural tube closure defect. In contrast, inhibiting the electron transport chain did not affect neural tube formation. Furthermore, inhibiting glycolysis affected cell proliferation, but not differentiation and survival. Inhibiting glycolysis repressed the phosphorylation of myosin light chain 2, and consequent neural plate folding. Our findings revealed that anaerobic glycolysis regulates neuroepithelial cell proliferation and apical constriction during the early phase of neural tube closure.
生理性缺氧对胎盘哺乳动物的发育至关重要。然而，缺氧调节胚胎发育的潜在机制仍不清楚。我们发现，糖酵解基因的表达部分依赖于E8.25小鼠胚胎神经上皮细胞中的缺氧状态。与这一发现一致，在神经管闭合早期（E8.0 - 8.5）抑制糖酵解会导致神经管闭合缺陷。相比之下，抑制电子传递链并不影响神经管形成。此外，抑制糖酵解影响细胞增殖，但不影响细胞分化和存活。抑制糖酵解会抑制肌球蛋白轻链2的磷酸化，从而影响神经板折叠。我们的研究结果表明，无氧糖酵解在神经管闭合早期调节神经上皮细胞增殖和顶端收缩。
