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Molecular and Cellular Biology, December 2006, p. 8880-8891, Vol. 26, No. 23
0270-7306/06/$08.00+0     doi:10.1128/MCB.00751-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Ribosomal Protein S6 Gene Haploinsufficiency Is Associated with Activation of a p53-Dependent Checkpoint during Gastrulation ^,

Linda Pani,¹ Sanda Tamarut,¹ Melanie Sticker-Jantscheff,² Martina Barki,¹ Davor Solter,³ Miljana Uzelac,¹ Kristina Grabui,¹ and Sinia Volarevi^1*

Department of Molecular Medicine and Biotechnology, School of Medicine, University of Rijeka, Rijeka, Croatia,¹ Institute of Cell Biology, Swiss Federal Institute of Technology (ETH), Zurich, Switzerland,² Department of Developmental Biology, Max Planck Institute of Immunobiology, Freiburg, Germany³

Received 1 May 2006/ Returned for modification 18 June 2006/ Accepted 15 September 2006

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.

Published ahead of print on 25 September 2006.

Supplemental material for this article may be found at http://mcb.asm.org/.

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