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EMBO Rep. 2015 Aug;16(8):1005-21. doi: 10.15252/embr.201540162. Epub 2015 Jul 3.

Venus trap in the mouse embryo reveals distinct molecular dynamics underlying specification of first embryonic lineages.

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Developmental Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
School of Life Sciences Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Max Planck Institute for Molecular Biomedicine, Muenster, Germany.
Developmental Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany


Mammalian development begins with the segregation of embryonic and extra-embryonic lineages in the blastocyst. Recent studies revealed cell-to-cell gene expression heterogeneity and dynamic cell rearrangements during mouse blastocyst formation. Thus, mechanistic understanding of lineage specification requires quantitative description of gene expression dynamics at a single-cell resolution in living embryos. However, only a few fluorescent gene expression reporter mice are available and quantitative live image analysis is limited so far. Here, we carried out a fluorescence gene-trap screen and established reporter mice expressing Venus specifically in the first lineages. Lineage tracking, quantitative gene expression and cell position analyses allowed us to build a comprehensive lineage map of mouse pre-implantation development. Our systematic analysis revealed that, contrary to the available models, the timing and mechanism of lineage specification may be distinct between the trophectoderm and the inner cell mass. While expression of our trophectoderm-specific lineage marker is upregulated in outside cells upon asymmetric divisions at 8- and 16-cell stages, the inside-specific upregulation of the inner-cell-mass marker only becomes evident at the 64-cell stage. This study thus provides a framework toward systems-level understanding of embryogenesis marked by high dynamicity and stochastic variability.


gene trap; lineage map; live imaging; mouse; pre‐implantation development

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