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Maternally and zygotically provided Cdx2 have novel and critical roles for early development of the mouse embryo

Jedrusik, Agnieszka and Bruce, Alexander W. and Tan, Meng H. and Leong, Denise E. and Skamagki, Maria and Yao, Mylene and Zernicka-Goetz, Magdalena (2010) Maternally and zygotically provided Cdx2 have novel and critical roles for early development of the mouse embryo. Developmental Biology, 344 (1). pp. 66-78. ISSN 0012-1606. PMCID PMC2954319. https://resolver.caltech.edu/CaltechAUTHORS:20190417-163114755

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Abstract

Divisions of polarised blastomeres that allocate polar cells to outer and apolar cells to inner positions initiate the first cell fate decision in the mouse embryo. Subsequently, outer cells differentiate into trophectoderm while inner cells retain pluripotency to become inner cell mass (ICM) of the blastocyst. Elimination of zygotic expression of trophectoderm-specific transcription factor Cdx2 leads to defects in the maintenance of the blastocyst cavity, suggesting that it participates only in the late stage of trophectoderm formation. However, we now find that mouse embryos also have a maternally provided pool of Cdx2 mRNA. Moreover, depletion of both maternal and zygotic Cdx2 from immediately after fertilization by three independent approaches, dsRNAi, siRNAi and morpholino oligonucleotides, leads to developmental arrest at much earlier stages than expected from elimination of only zygotic Cdx2. This developmental arrest is associated with defects in cell polarisation, reflected by expression and localisation of cell polarity molecules such as Par3 and aPKC and cell compaction at the 8- and 16-cell stages. Cells deprived of Cdx2 show delayed development with increased cell cycle length, irregular cell division and increased incidence of apoptosis. Although some Cdx2-depleted embryos initiate cavitation, the cavity cannot be maintained. Furthermore, expression of trophectoderm-specific genes, Gata3 and Eomes, and also the trophectoderm-specific cytokeratin intermediate filament, recognised by Troma1, are greatly reduced or undetectable. Taken together, our results indicate that Cdx2 participates in two steps leading to trophectoderm specification: appropriate polarisation of blastomeres at the 8- and 16-cell stage and then the maintenance of trophectoderm lineage-specific differentiation.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1016/j.ydbio.2010.04.017DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2954319/PubMed CentralArticle
ORCID:
AuthorORCID
Zernicka-Goetz, Magdalena0000-0002-7004-2471
Additional Information:© 2010 Elsevier Inc. Open access under CC BY license. Received 21 July 2009, Revised 30 March 2010, Accepted 16 April 2010, Available online 27 April 2010. We are grateful to the Wellcome Trust, NIH HD057970 and HD01249 (M.W.M.Y.) for providing the funding which enabled this work, to Annett Hahn-Windgassen and Krzysztof Wicher for experimental help and discussions and to Brian Hendrich for sharing immuno-cytochemical protocol. The Troma-1 antibody developed by Philippe Brulet and Rolf Kemler was obtained from the Developmental Studies Hybridoma Bank developed under the auspices of the NICHD and maintained by The University of Iowa, Department of Biology, Iowa City, IA 52242.
Funders:
Funding AgencyGrant Number
Wellcome TrustUNSPECIFIED
NIHHD057970
NIHHD01249
Subject Keywords:Cdx2; Trophectoderm; Mouse embryo; Polarisation; Cell death; Compaction
Issue or Number:1
PubMed Central ID:PMC2954319
Record Number:CaltechAUTHORS:20190417-163114755
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20190417-163114755
Official Citation:Agnieszka Jedrusik, Alexander W. Bruce, Meng H. Tan, Denise E. Leong, Maria Skamagki, Mylene Yao, Magdalena Zernicka-Goetz, Maternally and zygotically provided Cdx2 have novel and critical roles for early development of the mouse embryo, Developmental Biology, Volume 344, Issue 1, 2010, Pages 66-78, ISSN 0012-1606, https://doi.org/10.1016/j.ydbio.2010.04.017. (http://www.sciencedirect.com/science/article/pii/S0012160610002472)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:94771
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:18 Apr 2019 21:49
Last Modified:03 Oct 2019 21:07

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