Maternal origins of developmental reproducibility

Abstract: Cell fate decisions in multicellular organisms are precisely coordinated, leading to highly reproducible macroscopic outcomes of developmental processes. The origins of this reproducibility can be found at the molecular level during the earliest stages of development when spatial patterns of morphogen (form-generating) molecules emerge reproducibly. However, the initial conditions for these early stages are determined by the female during oogenesis, and it is unknown whether reproducibility is passed on to the zygote or whether it is reacquired by the zygote. Here we examine the earliest reproducible pattern in the Drosophila embryo, the Bicoid protein gradient. Using a unique combination of absolute molecule counting techniques, we show that it is generated from a highly controlled source of mRNA molecules that is reproducible from embryo to embryo to within ~8%. This occurs in a perfectly linear feed-forward process: changes in the female's gene dosage lead to proportional changes in the mRNA and protein counts in the embryo. In this setup, noise is kept low in the transition from one molecular species to another, allowing the female to precisely deposit the same absolute number of mRNA molecules in each embryo and therefore confer reproducibility to the Bicoid pattern. Our results indicate that the reproducibility of the morphological structures that emerge in the embryo originates during oogenesis when all initial patterning signals are controlled with precision similar to what we observe for the Bicoid pattern.