Positional information encoded in the dynamic differences between neighboring oscillators during vertebrate segmentation.

A central problem in developmental biology is to understand how cells interpret their positional information to give rise to spatial patterns, such as the process of periodic segmentation of the vertebrate embryo into somites. For decades, somite formation has been interpreted according to the clock-and-wavefront model. In this conceptual framework, molecular oscillators set the frequency of somite formation while the positional information is encoded in signaling gradients. Recent experiments using ex vivo explants have challenged this interpretation, suggesting that positional information is encoded in the properties of the oscillators, independent of long-range modulations such as signaling gradients. Here, we propose that positional information is encoded in the difference in the levels of neighboring oscillators. The differences gradually increase because both the amplitude and the period of the oscillators increase with time. When this difference exceeds a certain threshold, the segmentation program starts. Using this framework, we quantitatively fit experimental data from in vivo and ex vivo mouse segmentation, and propose mechanisms of somite scaling. Our results suggest a novel mechanism of spatial pattern formation based on the local interactions between dynamic molecular oscillators.