zernicka-goetz 2010

zernicka-goetz 2010 - Origin and formation of the rst two...

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Origin and formation of the rst two distinct cell types of the inner cell mass in the mouse embryo Samantha A. Morris a,b , Roy T. Y. Teo a,b,c , Huiliang Li e , Paul Robson c,d , David M. Glover f , and Magdalena Zernicka-Goetz a,b,1 a Wellcome Trust/Cancer Research UK Gurdon Institute, b Department of Physiology, Development and Neuroscience, and f Department of Genetics, University of Cambridge, Cambridge CB2 3EH, United Kingdom; c Stem Cell and Developmental Biology, Genome Institute of Singapore, Republic of Singapore 138672; d Department of Biological Sciences, National University of Singapore, Republic of Singapore 117543; and e Wolfson Institute for Biomedical Research and Department of Biology, University College London, London WC1E 6BT, Unitd Kingdom Edited* by John B. Gurdon, University of Cambridge, Cambridge, United Kingdom, and approved February 25, 2010 (received for review December 28, 2009) A crucial question in mammalian development is how cells of the early embryo differentiate into distinct cell types. The rst 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 pluri- potent and give rise to the epiblast, and hence the future body, whereas others develop into the primitive endoderm, an extraem- bryonic tissue. How the fate of these inside cells is decided is unknown: Is the process random, or is it related to their develop- mental 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 rst wave of asym- metric 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 endo- derm. Finally, with our ability to determine the origin of cells, we nd 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 preimplan- tation mouse embryo. cell fate | epiblast | primitive endoderm | Gata6 | Sox17 T he rst decision determining cell fate in the mouse embryo is taken when two populations of cells are physically partitioned by successive waves of asymmetric divisions commencing at the eight-cell stage (1 5). Cells positioned inside the embryo develop into the inner cell mass (ICM), whereas outside cells develop into the rst extraembryonic tissue, the trophectoderm, that will give rise to the placenta. The second decision determining cell fate
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This note was uploaded on 09/29/2010 for the course BIO 325 taught by Professor Bernadette-holdener,g during the Spring '08 term at SUNY Stony Brook.

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zernicka-goetz 2010 - Origin and formation of the rst two...

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