Ribosomal protein S6 gene haploinsufficiency is associated with activation of a p53-dependent checkpoint during gastrulation
Ribosomal protein S6 gene haploinsufficiency is associated with activation of a p53-dependent checkpoint during gastrulation
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DOI：
10.1128/mcb.00751-06
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发表时间：
2006-12-01
影响因子：
5.3
通讯作者：
Volarevic, Sinisa
中科院分区：
文献类型：
--
作者：
Panic, Linda;Tamarut, Sanda;Volarevic, Sinisa
细胞生长过程中需要新生核糖体生物合成。为了深入了解这一过程在小鼠卵子发生和胚胎发育过程中的重要性，我们删除了生长卵母细胞中核糖体蛋白 S6 基因的一个等位基因，并生成了 S6 杂合胚胎。直到胚胎第 5.5 天 (E5.5) 为止，卵子发生和胚胎发育均正常。然而，进入细胞周期 M 期和细胞凋亡的抑制在 E5.5 后变得明显，并导致原肠形成期间致死。 p53 的基因失活绕过了这个检查点并延长了发育直至 E12.5，此时胚胎死亡，显示 D 型细胞周期蛋白表达减少、胎儿肝脏红细胞生成减少和胎盘缺陷。因此，在原肠胚形成过程中，p53依赖性检查点被激活，以响应核糖体不足，以防止发育程序的不当执行。
Nascent ribosome biogenesis is required during cell growth. To gain insight into the importance of this process during mouse oogenesis and embryonic development, we deleted one allele of the ribosomal protein S6 gene in growing oocytes and generated S6-heterozygous embryos. Oogenesis and embryonic development until embryonic day 5.5 (E5.5) were normal. However, inhibition of entry into M phase of the cell cycle and apoptosis became evident post-E5.5 and led to perigastrulation lethality. Genetic inactivation of p53 bypassed this checkpoint and prolonged development until E12.5, when the embryos died, showing decreased expression of D-type cyclins, diminished fetal liver erythropoiesis, and placental defects. Thus, a p53-dependent checkpoint is activated during gastrulation in response to ribosome insufficiency to prevent improper execution of the developmental program.