A fundamental characteristic of all vertebrates is the metameric organization of their body plan, best exemplified by the vertebral column. This organization originates during embryonic development and the emergence of the vertebrae precursor, the somites, which form from the paraxial presomitic mesoderm (PSM). The discovery of oscillatory transcriptional activity of the Notch-signaling pathway within the PSM supports the existence of an embryological clock, the segmentation clock, which is responsible in controlling the periodic formation of somites. Here, I present the discovery of oscillatory mRNA expression of Axin2, a target of the Wnt-signaling pathway, in the PSM. This establishes a novel link between Wnt signaling and the segmentation clock. I then describe the generation of a two-photon, real-time imaging technology that allows visualizing segmentation clock activity in realtime in living mouse embryos. This enables us to directly measure oscillation parameters in the PSM. Finally, I describe the discovery of a -catenin protein gradient in the PSM. Using conditional gene targeting experiments, we establish that this gradient controls PSM maturation and differentiation. Moreover, this gradient represents a permissive signal that allows segmentation clock activity to occur. Based on the results presented, I propose a novel model for somite formation.
