Scalable Control of Developmental Timetables by Epigenetic Switching Networks

During development, progenitor cells follow timetables for differentiation that span many cell generations. These developmental timetables are robustly encoded by the embryo, yet scalably adjustable by evolution, facilitating variation in organism size and form. Epigenetic switches, involving rate-limiting activation steps at regulatory gene loci, control gene activation timing in diverse contexts, and could profoundly impact the dynamics of gene regulatory networks controlling developmental lineage specification. Here, we develop a mathematical framework to model regulatory networks with genes controlled by epigenetic switches. Using this framework, we show that such epigenetic switching networks uphold developmental timetables that robustly span many cell generations, and enable the generation of differentiated cells in precisely defined numbers and fractions. Changes to epigenetic switching networks can readily alter the timing of developmental events within a timetable, or alter the overall speed at which timetables unfold, enabling scalable control over differentiated population sizes. With their robust, yet flexibly adjustable nature, epigenetic switching networks could represent central targets on which evolution acts to manufacture diversity in organism size and form.