학술논문

Growth-factor-mediated coupling between lineage size and cell fate choice underlies robustness of mammalian development.
Document Type
Article
Source
eLife. 9/18/2020, p1-33. 33p.
Subject
*CELL size
*MAMMALIAN embryos
*LASER ablation
*COUPLES
*MATHEMATICAL models
Language
ISSN
2050-084X
Abstract
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. [ABSTRACT FROM AUTHOR]