Title: Distorted Development: noisy dynamics on Waddington’s epigenetic landscape

Abstract: During the development of multi-cellular organisms, such as humans, the right cell types arrive in their right numbers, at the right time, in the right place. The mechanisms that govern this process are nowhere near fully understood. What makes this even more puzzling is that the fundamental processes that drive and control cellular behaviour are random and to a large extent unpredictable. Despite this randomness, biological behaviour can be highly predictable with cells dividing and differentiating in a reproducible manner.
Here we explore this randomness and its ramifications in the context of Waddington’s epigenetic landscape. Here, cells are seen as marbles traversing down a landscape of valleys and hills with the valleys corresponding to distinct cell types; the lower a marble rolls downhill, the more distinct the cell becomes. Where valleys divide, the cell has the choice of attaining different fates. We show that the wrong (or right) type of noise shapes and distorts the landscape. Valleys can shift or disappear entirely. We discuss the role of this noise in the contexts of cell differentiation and of reverse-engineering regulatory programs.