engleski

Ribosomal protein S6 haploinsufficiency activates a p53-dependent checkpoint during gastrulation

Nascent ribosome biogenesis is required during cell growth. To gain insight into 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 E5.5 were normal. However, inhibition of entry into M phase of the cell cycle and apoptosis became evident post E5.5, leading to peri-gastrulation lethality. Genetic inactivation of p53 bypassed this checkpoint and prolonged development until E12.5, when they die with defective translation of D-type cyclins and erythropoiesis. Thus, a p53-dependent checkpoint is activated during gastrulation in response to ribosome insufficiency to prevent improper execution of the developmental program.

cell growth; ribosome; Rps6; gastrulation; p53; checkpoint

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