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Origin and formation of the first two distinct cell types of the inner cell mass in the mouse embryo

Morris, Samantha A. and Teo, Roy T. Y. and Li, Huiliang and Robson, Paul and Glover, David M. and Zernicka-Goetz, Magdalena (2010) Origin and formation of the first two distinct cell types of the inner cell mass in the mouse embryo. Proceedings of the National Academy of Sciences of the United States of America, 107 (14). pp. 6364-6369. ISSN 0027-8424. PMCID PMC2852013. doi:10.1073/pnas.0915063107. https://resolver.caltech.edu/CaltechAUTHORS:20190417-163114958

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Abstract

A crucial question in mammalian development is how cells of the early embryo differentiate into distinct cell types. The first decision is taken when cells undertake waves of asymmetric division that generate one daughter on the inside and one on the outside of the embryo. After this division, some cells on the inside remain pluripotent and give rise to the epiblast, and hence the future body, whereas others develop into the primitive endoderm, an extraembryonic tissue. How the fate of these inside cells is decided is unknown: Is the process random, or is it related to their developmental origins? To address this question, we traced all cells by live-cell imaging in intact, unmanipulated embryos until the epiblast and primitive endoderm became distinct. This analysis revealed that inner cell mass (ICM) cells have unrestricted developmental potential. However, cells internalized by the first wave of asymmetric divisions are biased toward forming pluripotent epiblast, whereas cells internalized in the next two waves of divisions are strongly biased toward forming primitive endoderm. Moreover, we show that cells internalized by the second wave up-regulate expression of Gata6 and Sox17, and changing the expression of these genes determines whether the cells become primitive endoderm. Finally, with our ability to determine the origin of cells, we find that inside cells that are mispositioned when they are born can sort into the correct layer. In conclusion, we propose a model in which the timing of cell internalization, cell position, and cell sorting combine to determine distinct lineages of the preimplantation mouse embryo.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1073/pnas.0915063107DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2852013/PubMed CentralArticle
http://www.pnas.org/cgi/content/full/0915063107/DCSupplementalPublisherSupporting Information
ORCID:
AuthorORCID
Glover, David M.0000-0003-0956-0103
Zernicka-Goetz, Magdalena0000-0002-7004-2471
Additional Information:© 2010 National Academy of Sciences. Edited by John B. Gurdon, University of Cambridge, Cambridge, United Kingdom, and approved February 25, 2010 (received for review December 28, 2009) We are grateful to Kat Hadjantonakis and Bill Richardson for sharing the transgenic lines, to Marko Hyvönen, Jonathon Pines, and to members of the Zernicka-Goetz laboratory for discussions. This work was supported by the Wellcome Trust. The authors declare no conflict of interest. This Direct Submission article had a prearranged editor. This article contains supplementary information online at www.pnas.org/cgi/content/full/0915063107/DCSupplemental. Note Added in Proof. While this paper was under review, complementary findings describing the role of Sox17 in directing cells towards the PE lineage have been reported (27).
Funders:
Funding AgencyGrant Number
Wellcome TrustUNSPECIFIED
Subject Keywords:cell fate; epiblast; primitive endoderm; Gata6; Sox17
Issue or Number:14
PubMed Central ID:PMC2852013
DOI:10.1073/pnas.0915063107
Record Number:CaltechAUTHORS:20190417-163114958
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20190417-163114958
Official Citation:Origin and formation of the first two distinct cell types of the inner cell mass in the mouse embryo Samantha A. Morris, Roy T. Y. Teo, Huiliang Li, Paul Robson, David M. Glover, Magdalena Zernicka-Goetz Proceedings of the National Academy of Sciences Apr 2010, 107 (14) 6364-6369; DOI: 10.1073/pnas.0915063107
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:94773
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:18 Apr 2019 21:36
Last Modified:16 Nov 2021 17:07

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