title: Maternal-zygotic knockout reveals a critical role of Cdx2 in the morula to blastocyst transition.
abstract: The first lineage segregation in the mouse embryo generates the inner cell mass (ICM), which gives rise to the pluripotent epiblast and therefore the future embryo, and the trophectoderm (TE), which will build the placenta. The TE lineage depends on the transcription factor Cdx2. However, when Cdx2 first starts to act remains unclear. Embryos with zygotic deletion of Cdx2 develop normally until the late blastocyst stage leading to the conclusion that Cdx2 is important for the maintenance but not specification of the TE. In contrast, down-regulation of Cdx2 transcripts from the early embryo stage results in defects in TE specification before the blastocyst stage. Here, to unambiguously address at which developmental stage Cdx2 becomes first required, we genetically deleted Cdx2 from the oocyte stage using a Zp3-Cre/loxP strategy. Careful assessment of a large cohort of Cdx2 maternal-zygotic null embryos, all individually filmed, examined and genotyped, reveals an earlier lethal phenotype than observed in Cdx2 zygotic null embryos that develop until the late blastocyst stage. The developmental failure of Cdx2 maternal-zygotic null embryos is associated with cell death and failure of TE specification, starting at the morula stage. These results indicate that Cdx2 is important for the correct specification of TE from the morula stage onwards and that both maternal and zygotic pools of Cdx2 are required for correct pre-implantation embryogenesis.
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Site, Cambridge CB2 3DY, UK.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Jedrusik
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Site, Cambridge CB2 3DY, UK.
authors.forename: Andy
authors.initials: A
authors.lastname: Cox
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Site, Cambridge CB2 3DY, UK.
authors.forename: Krzysztof B
authors.initials: KB
authors.lastname: Wicher
authors.affiliation: Department of Genetics, University of Cambridge, Downing Site, Cambridge CB2 3EH, UK.
authors.forename: David M
authors.initials: DM
authors.lastname: Glover
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Site, Cambridge CB2 3DY, UK.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Zernicka-Goetz
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000166:cytology* / Q000378:metabolism; D019521:Body Patterning; D001947:Breeding; D000071616:CDX2 Transcription Factor; D016923:Cell Death; D004475:Ectoderm / Q000166:cytology / Q000378:metabolism; D047108:Embryonic Development; D005260:Female; D055786:Gene Knockout Techniques; D018398:Homeodomain Proteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D009028:Morula / Q000166:cytology* / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency / Q000378:metabolism*; D015053:Zygote / Q000166:cytology / Q000378:metabolism*
chemical_list: D000071616:CDX2 Transcription Factor; C487514:Cdx2 protein, mouse; D018398:Homeodomain Proteins; D014157:Transcription Factors
keywords: Cdx2; Maternal-zygotic knockout; Mouse embryo; Trophectoderm