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

Cell. 2017 Oct 19;171(3):668-682.e11. doi: 10.1016/j.cell.2017.08.043. Epub 2017 Sep 21.

Abstract

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.

Keywords: Notch; Yap; clock; excitability; excitable system; oscillations; presomitic mesoderm; segmentation; somitogenesis.

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Biological Clocks*
  • Cell Cycle Proteins
  • Chick Embryo
  • Embryo, Mammalian / metabolism
  • Embryo, Nonmammalian / metabolism
  • Mesoderm / metabolism
  • Mice
  • Morphogenesis
  • Phosphoproteins / metabolism
  • Quorum Sensing
  • Signal Transduction*
  • Somites / metabolism
  • YAP-Signaling Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins
  • Phosphoproteins
  • YAP-Signaling Proteins
  • Yap1 protein, mouse