TY - JOUR TI - Growth-factor-mediated coupling between lineage size and cell fate choice underlies robustness of mammalian development AU - Saiz, Néstor AU - Mora-Bitria, Laura AU - Rahman, Shahadat AU - George, Hannah AU - Herder, Jeremy P AU - Garcia-Ojalvo, Jordi AU - Hadjantonakis, Anna-Katerina A2 - Robertson, Elizabeth A2 - Barkai, Naama A2 - Maître, Jean-Léon VL - 9 PY - 2020 DA - 2020/07/28 SP - e56079 C1 - eLife 2020;9:e56079 DO - 10.7554/eLife.56079 UR - https://doi.org/10.7554/eLife.56079 AB - Precise control and maintenance of population size is fundamental for organismal development and homeostasis. The three cell types of the mammalian blastocyst are generated in precise proportions over a short time, suggesting a mechanism to ensure a reproducible outcome. We developed a minimal mathematical model demonstrating growth factor signaling is sufficient to guarantee this robustness and which anticipates an embryo's response to perturbations in lineage composition. Addition of lineage-restricted cells both in vivo and in silico, causes a shift of the fate of progenitors away from the supernumerary cell type, while eliminating cells using laser ablation biases the specification of progenitors toward the targeted cell type. Finally, FGF4 couples fate decisions to lineage composition through changes in local growth factor concentration, providing a basis for the regulative abilities of the early mammalian embryo whereby fate decisions are coordinated at the population level to robustly generate tissues in the right proportions. KW - mouse embryo KW - cell fate KW - imaging KW - blastocyst KW - cell numbers KW - modeling JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -