Conditional Aurora A deficiency differentially affects early mouse embryo patterning

• Published in: Developmental biology 2012-11, Vol.371 (1), p.77-85
• Main Authors: Yoon, Yeonsoo, Cowley, Dale O., Gallant, Judith, Jones, Stephen N., Van Dyke, Terry, Rivera-Pérez, Jaime A.
• Format: Article
• Language: English
• Subjects: Animals; apoptosis; Apoptosis - genetics; Aurora A; Aurora Kinase A; Aurora Kinases; beta-Galactosidase; blastocyst; Body Patterning - genetics; cell proliferation; conceptus; developmental stages; DNA Primers - genetics; Embryo; Embryo, Mammalian - embryology; Embryonic Stem Cells - metabolism; Endoderm - embryology; Epiblast; Fluorescent Antibody Technique; Gastrulation; Gene Knockout Techniques; Germ Layers - embryology; In Situ Hybridization; Mice; Mouse; mutants; mutation; organogenesis; Patterning; Protein-Serine-Threonine Kinases - deficiency; Protein-Serine-Threonine Kinases - genetics; resorption; stem cells; tissues; Visceral endoderm
• ISSN: 0012-1606; 1095-564X
• DOI: 10.1016/j.ydbio.2012.08.010

Aurora A is a mitotic kinase essential for cell proliferation. In mice, ablation of Aurora A results in mitotic arrest and pre-implantation lethality, preventing studies at later stages of development. Here we report the effects of Aurora A ablation on embryo patterning at early post-implantation stages. Inactivation of Aurora A in the epiblast or visceral endoderm layers of the conceptus leads to apoptosis and inhibition of embryo growth, causing lethality and resorption at approximately E9.5. The effects on embryo patterning, however, depend on the tissue affected by the mutation. Embryos with an epiblast ablation of Aurora A properly establish the anteroposterior axis but fail to progress through gastrulation. In contrast, mutation of Aurora A in the visceral endoderm, leads to posteriorization of the conceptus or failure to elongate the anteroposterior axis. Injection of ES cells into Aurora A epiblast knockout blastocysts reconstitutes embryonic development to E9.5, indicating that the extra-embryonic tissues in these mutant embryos can sustain development to organogenesis stages. Our results reveal new ways to induce apoptosis and to ablate cells in a tissue-specific manner in vivo. Moreover, they show that epiblast-ablated embryos can be used to test the potency of stem cells. ► We ablate Aurora A in the epiblast or visceral endoderm of mouse embryos. ► Aurora A ablation leads to apoptosis, patterning defects and embryo lethality. ► ES cells can rescue the phenotype of Aurora A deficiency in the epiblast. ► Embryonic defects vary depending on the tissue affected by the mutation. ► We provide an alternative to tetraploid complementation experiments.