{[ promptMessage ]}

Bookmark it

{[ promptMessage ]}

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

Info icon This preview shows pages 1–2. Sign up to view the full content.

View Full Document Right Arrow Icon
Origin and formation of the fi 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 fi 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 fi 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 fi 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 fi 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 fi rst extraembryonic tissue, the trophectoderm, that will give rise to the placenta. The second decision determining cell fate
Image of page 1

Info icon This preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon
Image of page 2
This is the end of the preview. Sign up to access the rest of the document.

{[ snackBarMessage ]}

What students are saying

  • Left Quote Icon

    As a current student on this bumpy collegiate pathway, I stumbled upon Course Hero, where I can find study resources for nearly all my courses, get online help from tutors 24/7, and even share my old projects, papers, and lecture notes with other students.

    Student Picture

    Kiran Temple University Fox School of Business ‘17, Course Hero Intern

  • Left Quote Icon

    I cannot even describe how much Course Hero helped me this summer. It’s truly become something I can always rely on and help me. In the end, I was not only able to survive summer classes, but I was able to thrive thanks to Course Hero.

    Student Picture

    Dana University of Pennsylvania ‘17, Course Hero Intern

  • Left Quote Icon

    The ability to access any university’s resources through Course Hero proved invaluable in my case. I was behind on Tulane coursework and actually used UCLA’s materials to help me move forward and get everything together on time.

    Student Picture

    Jill Tulane University ‘16, Course Hero Intern