Positional information from oscillatory phase shifts : insights from in silico evolution.

Complex cellular decisions are based on temporal dynamics of pathways, including genetic oscillators. In development, recent works on vertebrae formation have suggested that relative phase of genetic oscillators encode positional information, including differentiation front defining vertebrae positions. Precise mechanisms for this are still unknown. Here, we use computational evolution to find gene network topologies that can compute the phase difference between oscillators and convert it into a decoder morphogen concentration. Two types of networks are discovered, based on symmetry properties of the decoder gene. So called asymmetric networks are studied, and two submodules are identified converting phase information into an amplitude variable. Those networks naturally display a 'shock' for a well defined phase difference, that can be used to define a wavefront of differentiation. We show how implementation of these ideas reproduce experimental features of vertebrate segmentation.