Travelling waves in somitogenesis: collective cellular properties emerge from time-delayed juxtacrine oscillation coupling

Abstract

AbstractThe sculpturing of the vertebrate body plan into segments begins with the sequential formation of somites in the presomitic mesoderm (PSM). The rhythmicity of this process is controlled by travelling waves of gene expression. These kinetic waves emerge from coupled cellular oscillators and sweep across the PSM. In zebrafish, the oscillations are driven by autorepression of her genes and are synchronized via Notch signalling. Mathematical modelling has played an important role in explaining how collective properties emerge from the molecular interactions. Increasingly more quantitative experimental data permits the validation of those mathematical models, yet leads to increasingly more complex model formulations that hamper an intuitive understanding of the underlying mechanisms. Here, we review previous efforts, and design a mechanistic model of the her1 oscillator, which represents the experimentally viable her7;hes6 double mutant. This genetically simplified system is ideally suited to conceptually recapitulate oscillatory entrainment and travelling wave formation, and to highlight open questions. It shows that three key parameters, the autorepression delay, the juxtacrine coupling delay, and the coupling strength, are sufficient to understand the emergence of the collective period, the collective amplitude, and the synchronization of neighbouring Her1 oscillators. Moreover, two spatiotemporal time delay gradients, in the autorepression and in the juxtacrine signalling, are required to explain the collective oscillatory dynamics and synchrony of PSM cells. The highlighted developmental principles likely apply more generally to other developmental processes, including neurogenesis and angiogenesis.