title: Asynchronous fate decisions by single cells collectively ensure consistent lineage composition in the mouse blastocyst.
abstract: Intercellular communication is essential to coordinate the behaviour of individual cells during organismal development. The preimplantation mammalian embryo is a paradigm of tissue self-organization and regulative development; however, the cellular basis of these regulative abilities has not been established. Here we use a quantitative image analysis pipeline to undertake a high-resolution, single-cell level analysis of lineage specification in the inner cell mass (ICM) of the mouse blastocyst. We show that a consistent ratio of epiblast and primitive endoderm lineages is achieved through incremental allocation of cells from a common progenitor pool, and that the lineage composition of the ICM is conserved regardless of its size. Furthermore, timed modulation of the FGF-MAPK pathway shows that individual progenitors commit to either fate asynchronously during blastocyst development. These data indicate that such incremental lineage allocation provides the basis for a tissue size control mechanism that ensures the generation of lineages of appropriate size.
authors.affiliation: Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.
authors.forename: Néstor
authors.initials: N
authors.lastname: Saiz
authors.affiliation: Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.
authors.forename: Kiah M
authors.initials: KM
authors.lastname: Williams
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Hospital, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
authors.forename: Venkatraman E
authors.initials: VE
authors.lastname: Seshan
authors.affiliation: Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.
authors.forename: Anna-Katerina
authors.initials: AK
authors.lastname: Hadjantonakis
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000166:cytology* / Q000502:physiology*; D002454:Cell Differentiation; D019070:Cell Lineage; D046149:Embryo Culture Techniques; D047108:Embryonic Development; D005855:Germ Layers; D051379:Mice; D015398:Signal Transduction