Figure 1. Cells in different contexts: culture vs. embryo.

(A) Cells in culture require careful preparation to assure reproducibility across experiments. Female flies naturally prepare embryos in a high-throughput and reproducible manner. (B) Culturing allows examination of gene regulatory network behavior across a range of conditions in a synthetic environment. As such, it is not a priori evident which part of observed cell-to-cell variability (which can range between 50% and 500%) is due to sample preparation versus inherent fluctuations in the system. Studies of embryos reveal the degree of natural variability in gene expression that is tolerated by an intact system. As a system, the embryo is designed to generate a specific gene expression pattern within tight temporal and spatial constraints. This tight control results in levels of gene expression that can be reproducible within 10% and boundary positions with a 1% egg length reproducibility. (C) The absence of membranes between nuclei in the early embryo allows for the mixing of regulatory factors by diffusion. (D) Synchrony of the cell cycle is hardwired in the early fly developmental program. (E) Titrating input concentrations of transcription factors in cell culture requires the implementation of synthetic inducible circuits in multiple experiments. By contrast, transcription factor gradients in the early embryo span the natural range of patterning dynamics required for proper development.