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

Jedrusik, Agnieszka and Cox, Andy and Wicher, Krzysztof B. and Glover, David M. and Zernicka-Goetz, Magdalena (2015) Maternal-zygotic knockout reveals a critical role of Cdx2 in the morula to blastocyst transition. Developmental Biology, 398 (2). pp. 147-152. ISSN 0012-1606. PMCID PMC4319684. doi:10.1016/j.ydbio.2014.12.004. https://resolver.caltech.edu/CaltechAUTHORS:20190405-170316054

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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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1016/j.ydbio.2014.12.004DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4319684/PubMed CentralArticle
ORCID:
AuthorORCID
Glover, David M.0000-0003-0956-0103
Zernicka-Goetz, Magdalena0000-0002-7004-2471
Additional Information:© 2014 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/) Received 5 December 2014, Accepted 6 December 2014, Available online 13 December 2014. We are very grateful to Prof. Klaus Kaestner for Cdx2^(loxP) line and Maryna Panamarova for immunostaining mouse TS cells. We also thank our colleagues in the lab for valuable comments throughout the course of this work and the Wellcome Trust (Grant no. 098287/Z/12/Z) for supporting it.
Funders:
Funding AgencyGrant Number
Wellcome Trust098287/Z/12/Z
Subject Keywords:Mouse embryo; Cdx2; Maternal-zygotic knockout; Trophectoderm
Issue or Number:2
PubMed Central ID:PMC4319684
DOI:10.1016/j.ydbio.2014.12.004
Record Number:CaltechAUTHORS:20190405-170316054
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20190405-170316054
Official Citation:Agnieszka Jedrusik, Andy Cox, Krzysztof B. Wicher, David M. Glover, Magdalena Zernicka-Goetz, Maternal-zygotic knockout reveals a critical role of Cdx2 in the morula to blastocyst transition, Developmental Biology, Volume 398, Issue 2, 2015, Pages 147-152, ISSN 0012-1606, https://doi.org/10.1016/j.ydbio.2014.12.004. (http://www.sciencedirect.com/science/article/pii/S0012160614006307)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:94546
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:09 Apr 2019 15:52
Last Modified:16 Nov 2021 17:05

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