Excitable Dynamics and Yap-Dependent Mechanical Cues Drive the Segmentation Clock

The periodic segmentation of the vertebrate body axis into somites, and later vertebrae, relies on a genetic oscillator (the segmentation clock) driving the rhythmic activity of signaling pathways in the presomitic mesoderm (PSM). To understand whether oscillations are an intrinsic property of individual cells or represent a population-level phenomenon, we established culture conditions for stable oscillations at the cellular level. This system was used to demonstrate that oscillations are a collective property of PSM cells that can be actively triggered in vitro by a dynamical quorum sensing signal involving Yap and Notch signaling. Manipulation of Yap-dependent mechanical cues is sufficient to predictably switch isolated PSM cells from a quiescent to an oscillatory state in vitro, a behavior reminiscent of excitability in other systems. Together, our work argues that the segmentation clock behaves as an excitable system, introducing a broader paradigm to study such dynamics in vertebrate morphogenesis.