Laboratory for the Physics of Life Thomas Gregor, Professor of Physics, Princeton University

Cell fate decisions during multicellular development are precisely coordinated, leading to highly reproducible macroscopic structural outcomes [1-3]. The origins of this reproducibility are found at the molecular level during the earliest stages of development, when patterns of morphogen molecules emerge reproducibly [4, 5]. However, while the initial conditions for these early stages are determined by the female during oogenesis, it is unknown whether reproducibility is perpetuated from oogenesis or reacquired by the zygote. To address this issue in the early Drosophila embryo, we sought to count individual maternally deposited bicoid mRNA molecules and compare variability between embryos with previously observed fluctuations in the Bicoid protein gradient [6, 7]. Here we develop independent methods to quantify total amounts of mRNA in individual embryos and show that mRNA counts are highly reproducible between embryos to within ~9%, matching the reproducibility of the protein gradient. Reproducibility emerges from perfectly linear feed-forward processes: changing the genetic dosage in the female leads to proportional changes in the mRNA and protein numbers in the embryo. Our results indicate that the reproducibility of the morphological structures of embryos originates during oogenesis when initial patterning signals are precisely controlled.