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How cells coordinate their dynamic gene expression to produce patterns that transcend to the tissue scale is a fundamental question in biology. In the context of somitogenesis, the timing of segmentation is controlled by a molecular oscillator, the segmentation clock. The segmentation clock oscillations, particularly those regulated by Notch signaling, exhibit traveling wave patterns in the presomitic mesoderm (PSM) due to phase shifted oscillations along the AP axis. How their spatiotemporal dynamics are coordinated to produce such patterns is not fully understood. I first describe the origin of the traveling waves, with data obtained by imaging the onset of segmentation clock dynamics, at the gastrulating stages of the mouse embryo. Detailed analysis of the oscillations revealed that they are initially synchronous across space at its onset, but accumulate spatial phase shift over the first 6+ cycles, thereby leading to the emergence of traveling wave patterns. Such an accumulation of spatial phase shift agrees with the presence of a period gradient, where period mismatches between adjacent tissue increase the lag in oscillation phase over time. The existence of an oscillation period gradient has been reported in the later stages of the embryo across species, but not much is known about its regulation. FGF and Wnt signaling gradients present in the PSM have been nominated to control oscillation dynamics. However, past studies have reported that FGF signaling does not affect the segmentation clock, as segmentation pace was unaltered when FGF signaling was perturbed. Using an in vitro model of the PSM also showing an emergence of traveling waves, I characterized the effect of exogenous FGF signal on the wave dynamics in detail. The series of spatially and temporally designed FGF addition experiments indicate that FGF signaling governs the rate of change in oscillation period, or biologically, the rate of cellular maturation towards differentiation. Taken together, I uncover a novel role of FGF signaling in regulating spatiotemporal dynamics of segmentation clock oscillations in the mouse presomitic mesoderm.

Somites are periodically formed by segmentation of the anterior parts of the presomitic mesoderm (PSM). In the mouse embryo, this periodicity is controlled by the segmentation clock gene Hes7, which exhibits wave-like oscillatory expression in the PSM. Despite intensive studies, the exact mechanism of such synchronous oscillatory dynamics of Hes7 expression still remains to be analyzed. Detailed analysis of the segmentation clock has been hampered because it requires the use of live embryos, and establishment of an in vitro culture system would facilitate such analyses. Here, we established a simple and efficient method to generate mouse ES cell-derived PSM-like tissues, in which Hes7 expression oscillates like traveling waves. In these tissues, Hes7 oscillation is synchronized between neighboring cells, and the posterior-anterior axis is self-organized as the central-peripheral axis. This method is applicable to chemical-library screening and will facilitate the analysis of the molecular nature of the segmentation clock.