title: Venus trap in the mouse embryo reveals distinct molecular dynamics underlying specification of first embryonic lineages.
abstract: 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.
authors.affiliation: Developmental Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
authors.forename: Jens-Erik
authors.initials: JE
authors.lastname: Dietrich
authors.affiliation: Developmental Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Panavaite
authors.affiliation: Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Gunther
authors.affiliation: Developmental Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Wennekamp
authors.affiliation: School of Life Sciences Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
authors.forename: Anna C
authors.initials: AC
authors.lastname: Groner
authors.affiliation: Max Planck Institute for Molecular Biomedicine, Muenster, Germany.
authors.forename: Anton
authors.initials: A
authors.lastname: Pigge
authors.affiliation: Developmental Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Salvenmoser
authors.affiliation: School of Life Sciences Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
authors.forename: Didier
authors.initials: D
authors.lastname: Trono
authors.affiliation: Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Hufnagel
authors.affiliation: Developmental Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany hiiragi@embl.de.
authors.forename: Takashi
authors.initials: T
authors.lastname: Hiiragi
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000502:physiology*; D019070:Cell Lineage; D010064:Embryo Implantation; D047108:Embryonic Development; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D000069416:Intravital Microscopy; D051379:Mice
keywords: gene trap; lineage map; live imaging; mouse; pre‐implantation development