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Maternal-zygotic knockout reveals a critical role of Cdx2 in the morula to blastocyst transition.


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Authors

Jedrusik, Agnieszka 
Cox, Andy 
Wicher, Krzysztof B 
Glover, David M 
Zernicka-Goetz, Magdalena  ORCID logo  https://orcid.org/0000-0002-7004-2471

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.

Description

Keywords

Cdx2, Maternal-zygotic knockout, Mouse embryo, Trophectoderm, Animals, Blastocyst, Body Patterning, Breeding, CDX2 Transcription Factor, Cell Death, Ectoderm, Embryonic Development, Female, Gene Knockout Techniques, Homeodomain Proteins, Male, Mice, Morula, Transcription Factors, Zygote

Journal Title

Dev Biol

Conference Name

Journal ISSN

0012-1606
1095-564X

Volume Title

398

Publisher

Academic Press Inc.
Sponsorship
Wellcome Trust (098287/Z/12/Z)
Medical Research Council (G1001696)
Cancer Research Uk (None)
We thank the Wellcome Trust (Grant no. 098287/Z/12/Z) for supporting this work.