Ribosomal protein S6 gene haploinsufficiency is associated with activation of a p53-dependent checkpoint during gastrulation.
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.
Panić
Linda
L
Department of Molecular Medicine and Biotechnology, School of Medicine, University of Rijeka, Braće Branchetta 20, 51000, Rijeka, Croatia.
Tamarut
Sanda
S
Sticker-Jantscheff
Melanie
M
Barkić
Martina
M
Solter
Davor
D
Uzelac
Miljana
M
Grabusić
Kristina
K
Volarević
Sinisa
S
D000818:Animals; D001755:Blastocyst / Q000166:cytology; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D005775:Gastrula / Q000502:physiology*; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D011247:Pregnancy; D038601:Ribosomal Protein S6 / Q000235:genetics* / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D038601:Ribosomal Protein S6; D016159:Tumor Suppressor Protein p53; C448579:ribosomal protein S6, mouse