Walsh D, Li K, Wass J, Dolnikov A, Zeng F, Zhe L, Edwards M
Department of Veterinary Clinical Sciences, University of Sydney, New South Wales, Australia.
Dev Genet. 1993;14(2):127-36. doi: 10.1002/dvg.1020140207.
Synchronized regulation of cell division during gastrulation is essential for the regional proliferation of cells and pattern formation of the early CNS. The neural plate and neuroectoderm cells are a rapidly dividing and differentiating population of cells with a unique and rapid heat-shock response. Heat shock and the heat-shock genes were studied during neural plate development in a whole rat embryo culture system at 9.5-11.5 days. A lethal shock can cause cell death and severe developmental defects to the forebrain and eye during organogenesis. Heat shock can also result in acquired thermotolerance whereby cell progression is delayed at the G1/S and S/G2 boundaries of the cell cycle. This delay in cell cycle progression caused an overall lengthening of the cell cycle time of at least 2 hr. The heat shock genes may therefore function as cell cycle regulators in neuroectoderm induction and differentiation. The kinetics and expression of the hsp genes were examined in neuroectodermal cells by flow cytometry and Northern analysis. The levels of hsp mRNA 27, 71, 73, and 88 were identified following exposure at 42 degrees C (nonlethal), 43 degrees C (lethal) and 42 degrees/43 degrees C (thermotolerant) heat shock. Examination of hsp gene expression in the neural plate showed tight regulation in the cell cycle phases. Hsp 88 expression was enhanced at Go and hsp71 induction at G2 + M of the cell cycle. Cells exposed to a thermotolerant heat shock of 42 degrees C induced hsp71 mRNA expression in all phases of the cell cycle with the mRNA levels of hsp27, 73, and 88 increased but relatively constant. Following a lethal heat shock, dramatic changes in hsp expression were seen especially enhanced hsp71 induction in late S phase. The regulated expression of hsps during the cell cycle at various phases could play a unique and important role in the fate and recovery of neuroectoderm cells during early mammalian embryo development.
原肠胚形成期间细胞分裂的同步调节对于细胞的区域增殖和早期中枢神经系统的模式形成至关重要。神经板和神经外胚层细胞是一群快速分裂和分化的细胞，具有独特且快速的热休克反应。在9.5 - 11.5天的全大鼠胚胎培养系统中，研究了神经板发育过程中的热休克和热休克基因。致死性休克可导致器官发生期间前脑和眼睛的细胞死亡及严重发育缺陷。热休克还可导致获得性耐热性，从而使细胞进程在细胞周期的G1/S和S/G2边界处延迟。这种细胞周期进程的延迟导致细胞周期时间总体延长至少2小时。因此，热休克基因可能在神经外胚层诱导和分化中作为细胞周期调节因子发挥作用。通过流式细胞术和Northern分析检测了神经外胚层细胞中热休克蛋白基因的动力学和表达。在42℃（非致死）、43℃（致死）和42℃/43℃（耐热）热休克处理后，鉴定了hsp 27、71、73和88的mRNA水平。对神经板中热休克蛋白基因表达的检测显示在细胞周期阶段存在严格调控。hsp 88在G0期表达增强，hsp71在细胞周期的G2 + M期诱导表达。暴露于42℃耐热性热休克的细胞在细胞周期的所有阶段均诱导hsp71 mRNA表达，hsp27、73和88的mRNA水平升高但相对恒定。致死性热休克后，热休克蛋白表达出现显著变化，尤其是在S期后期hsp71诱导增强。热休克蛋白在细胞周期不同阶段的调控表达可能在早期哺乳动物胚胎发育过程中神经外胚层细胞的命运和恢复中发挥独特而重要的作用。
