PT  - JOURNAL ARTICLE
AU  - Néstor Saiz
AU  - Laura Mora-Bitria
AU  - Shahadat Rahman
AU  - Hannah George
AU  - Jeremy P Herder
AU  - Jordi García-Ojalvo
AU  - Anna-Katerina Hadjantonakis
TI  - Growth factor-mediated coupling between lineage size and cell fate choice underlies robustness of mammalian development
AID  - 10.1101/2019.12.27.889006
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 2019.12.27.889006
4099  - http://biorxiv.org/content/early/2019/12/27/2019.12.27.889006.short
4100  - http://biorxiv.org/content/early/2019/12/27/2019.12.27.889006.full
AB  - Precise control and maintenance of the size of cell populations is fundamental for organismal development and homeostasis. The three cell types that comprise the mammalian blastocyst-stage embryo are generated in precise proportions and in a short time, suggesting a size control mechanism ensures a reproducible outcome. Guided by experimental observations, we have developed a minimal mathematical model that explains how growth factor signaling is sufficient to guarantee this robustness. Using laser cell ablation to alter lineage composition in mouse blastocysts we show that cell elimination biases the specification of progenitors towards the targeted cell type, both in vivo and in silico. Conversely, introduction of supernumerary, lineage-restricted cells shifts the fate of progenitors away from that cell type. Finally, by controlling lineage specification in a growth factor-depleted context we show that FGF4 couples cell behaviors with lineage size. Our results reveal how individual cell fate decisions are coordinated in an in vivo self-organizing system to robustly generate tissues of appropriate size providing a basis for the regulative abilities of the mammalian embryo.