Self-Organization of Embryonic Genetic Oscillators into Spatiotemporal Wave Patterns

Charisios D Tsiairis,Alexander Aulehla

doi:10.1016/j.cell.2016.01.028

Abstract

SummaryIn vertebrate embryos, somites, the precursor of vertebrae, form from the presomitic mesoderm (PSM), which is composed of cells displaying signaling oscillations. Cellular oscillatory activity leads to periodic wave patterns in the PSM. Here, we address the origin of such complex wave patterns. We employed an in vitro randomization and real-time imaging strategy to probe for the ability of cells to generate order from disorder. We found that, after randomization, PSM cells self-organized into several miniature emergent PSM structures (ePSM). Our results show an ordered macroscopic spatial arrangement of ePSM with evidence of an intrinsic length scale. Furthermore, cells actively synchronize oscillations in a Notch-signaling-dependent manner, re-establishing wave-like patterns of gene activity. We demonstrate that PSM cells self-organize by tuning oscillation dynamics in response to surrounding cells, leading to collective synchronization with an average frequency. These findings reveal emergent properties within an ensemble of coupled genetic oscillators.

Highlights

A fundamental question in biology concerns the origin of ordered patterns
Our findings show that the fundamental dynamic properties of in vivo presomitic mesoderm (PSM) are fully recapitulated in emergent PSM structures (ePSM) and originate in a self-organized manner
We used fluorescence-activated cell sorting (FACS) of PSM cells carrying the LuVeLu reporter to sort cells based on peak or trough intensity values (Figures 5A, 5B, and S5)

Summary

Introduction

A fundamental question in biology concerns the origin of ordered patterns. One naturalistic answer that traces the ultimate cause within the living system is self-organization. Self-organized systems achieve order through the properties and interactions of their elements, without the requirement of external guidance. Such systems are abundant at any level of the organization of life (Camazine, 2003). Populations of fireflies self-organize and display synchronized flashing (Buck and Buck, 1966). In this case, each animal is an oscillator that adjusts its own rhythm according to the flashing of the neighbors, leading to a common rhythm (Mirollo and Strogatz, 1990). Temporal self-organization emerges from the interactions of coupled oscillators

Results

Discussion

Conclusion