Document Detail

Origin and formation of the first two distinct cell types of the inner cell mass in the mouse embryo.
MedLine Citation:
PMID:  20308546     Owner:  NLM     Status:  MEDLINE    
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.
Samantha A Morris; Roy T Y Teo; Huiliang Li; Paul Robson; David M Glover; Magdalena Zernicka-Goetz
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-03-22
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  107     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-04-07     Completed Date:  2010-05-05     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  6364-9     Citation Subset:  IM    
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MeSH Terms
Blastocyst / cytology
Cell Lineage*
Cell Movement
Cell Size
Embryo, Mammalian / cytology*,  metabolism
GATA6 Transcription Factor / genetics,  metabolism
Gene Expression Regulation, Developmental
HMGB Proteins / genetics,  metabolism
SOXF Transcription Factors / genetics,  metabolism
Grant Support
064421//Wellcome Trust; G0800784//Medical Research Council; //Wellcome Trust
Reg. No./Substance:
0/GATA6 Transcription Factor; 0/Gata6 protein, mouse; 0/HMGB Proteins; 0/SOXF Transcription Factors; 0/Sox17 protein, mouse

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