Abstract
A critical event in mammalian embryo development is construction of an inner cell mass surrounded by a trophoectoderm (a shell of cells that later form extraembryonic structures). We utilize multi-scale, stochastic modeling to investigate the design principles responsible for robust establishment of these structures. This investigation makes three predictions, each supported by our quantitative imaging. First, stochasticity in the expression of critical genes promotes cell plasticity and has a critical role in accurately organizing the developing mouse blastocyst. Second, asymmetry in the levels of noise variation (expression fluctuation) of Cdx2 and Oct4 provides a means to gain the benefits of noise-mediated plasticity while ameliorating the potentially detrimental effects of stochasticity. Finally, by controlling the timing and pace of cell fate specification, the embryo temporally modulates plasticity and creates a time window during which each cell can continually read its environment and adjusts its fate. These results suggest noise has a crucial role in maintaining cellular plasticity and organizing the blastocyst.
Highlights
A central question of developmental biology is how a single cell gives rise to an organism of exquisite complexity
A critical event in mammalian embryo development is construction of a mass of embryonic stem cells surrounded by a distinct shell that later forms the placenta along with other structures
Multiple hypotheses for what is responsible for this organization persist and it remains unclear what is responsible for the robust organization of these structures
Summary
A central question of developmental biology is how a single cell gives rise to an organism of exquisite complexity. Each cell of the early cleavage stage embryo is considered to be totipotent After compaction, these cells differentiate to become either the inner cell mass (ICM), which mainly gives rise to the future embryo, or the trophectoderm (TE), which forms extra-embryonic structures. These cells differentiate to become either the inner cell mass (ICM), which mainly gives rise to the future embryo, or the trophectoderm (TE), which forms extra-embryonic structures This lineage divergence is the first differentiation event in mammalian development, and is an intensely studied process in mammalian reproductive biology [1, 2]. These findings imply that a preimplantation mouse embryo interprets various types of information and coordinates the cellular response to produce a normal blastocyst
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