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Role of Cdx2 and cell polarity in cell allocation and specification of trophectoderm and inner cell mass in the mouse embryo

Jedrusik, Agnieszka and Parfitt, David-Emlyn and Guo, Guoji and Skamagki, Maria and Grabarek, Joanna B. and Johnson, Martin H. and Robson, Paul and Zernicka-Goetz, Magdalena (2008) Role of Cdx2 and cell polarity in cell allocation and specification of trophectoderm and inner cell mass in the mouse embryo. Genes and Development, 22 (19). pp. 2692-2706. ISSN 0890-9369. PMCID PMC2559904. doi:10.1101/gad.486108.

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Genesis of the trophectoderm and inner cell mass (ICM) lineages occurs in two stages. It is initiated via asymmetric divisions of eight- and 16-cell blastomeres that allocate cells to inner and outer positions, each with different developmental fates. Outside cells become committed to the trophectoderm at the blastocyst stage through Cdx2 activity, but here we show that Cdx2 can also act earlier to influence cell allocation. Increasing Cdx2 levels in individual blastomeres promotes symmetric divisions, thereby allocating more cells to the trophectoderm, whereas reducing Cdx2 promotes asymmetric divisions and consequently contribution to the ICM. Furthermore, both Cdx2 mRNA and protein levels are heterogeneous at the eight-cell stage. This heterogeneity depends on cell origin and has developmental consequences. Cdx2 expression is minimal in cells with unrestricted developmental potential that contribute preferentially to the ICM and is maximal in cells with reduced potential that contribute more to the trophectoderm. Finally, we describe a mutually reinforcing relationship between cellular polarity and Cdx2: Cdx2 influences cell polarity by up-regulating aPKC, but cell polarity also influences Cdx2 through asymmetric distribution of Cdx2 mRNA in polarized blastomeres. Thus, divisions generating inside and outside cells are truly asymmetric with respect to cell fate instructions. These two interacting effects ensure the generation of a stable outer epithelium by the blastocyst stage.

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Zernicka-Goetz, Magdalena0000-0002-7004-2471
Additional Information:© 2008, Cold Spring Harbor Laboratory Press. The Authors acknowledge that six months after the full-issue publication date, the Article will be distributed under a Creative Commons CC-BY-NC License (Attribution-NonCommercial 4.0 International License, Received May 5, 2008; revised version accepted August 6, 2008. This study is dedicated to Dr. Anne McLaren, a wonderful colleague and advisor, as a mark of respect for her work. We are grateful to Claire Chazaud for advice on in situ hybridization, Janet Rossant and David Glover for helpful discussion and comments on the manuscript, Kat Hadjantonakis and Ginny Papaioannou for reporter transgenic lines, and Jedrzej Chwiejczak for statistical analysis. This work has been supported by the Wellcome Trust Senior Research Fellowship and BBSRC grant to M.Z.G., and a Singapore Stem Cell Consortium grant to P.R. A.J. carried out experiments to modulate the Cdx2 expression levels. D.-E.P. examined the spatial distribution of Cdx2 protein and mRNA levels. G.G. and P.R. quantitatively analyzed levels of Cdx2, Oct4, Sall4, and Esrrb in blastomeres depending on their origin. M.S. carried out FISH experiments. J.G. participated in the blastomere collection to examine their expression profiles. M.H.J. cosupervised the project and contributed to writing. M.Z.-G. conceived, coordinated, and supervised the project, provided funding, and wrote the paper.
Funding AgencyGrant Number
Biotechnology and Biological Sciences Research Council (BBSRC)UNSPECIFIED
Singapore Stem Cell ConsortiumUNSPECIFIED
Subject Keywords:Cdx2; mouse embryo; polarization; ICM; blastocyst; trophectoderm
Issue or Number:19
PubMed Central ID:PMC2559904
Record Number:CaltechAUTHORS:20190418-150055370
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Official Citation:Role of Cdx2 and cell polarity in cell allocation and specification of trophectoderm and inner cell mass in the mouse embryo Agnieszka Jedrusik, David-Emlyn Parfitt, Guoji Guo, Maria Skamagki, Joanna B. Grabarek, Martin H. Johnson, Paul Robson, and Magdalena Zernicka-Goetz Genes Dev. October 1, 2008 22: 2692-2706; doi:10.1101/gad.486108
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:94795
Deposited By: George Porter
Deposited On:23 Apr 2019 17:35
Last Modified:16 Nov 2021 17:07

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