somite. In particular, the cyclic activation of the Notch pathway appears to be of great importance in the wavefront-clock model. It has been suggested that the activation of Notch cyclically activates a cascade of genes necessary for the somites to separate from the main paraxial body. This is controlled by different means in different species, such as through a simple negative feedback loop in zebrafish or in a complicated process in which FGF and Wnt clocks affect the Notch clock, as in chicks and mice. However, the segmentation clock model is highly evolutionarily conserved. Intrinsic expression of "clock genes" must oscillate with a periodicity equal to the time necessary for one somite to form, for example 30 minutes in zebrafish, 90 minutes in chicks, and 100 minutes in snakes. Gene oscillation in presomitic cells is largely, but not completely, cell-autonomous. When Notch signaling is disrupted in zebrafish, neighboring cells no longer oscillate synchronously, indicating that Notch signaling is important for keeping neighboring populations of cells synchronous. In addition, some cellular inter-dependency has been displayed in studies concerning the protein Sonic hedgehog (Shh) in somitogenesis. Although expression of Shh pathway proteins has not been reported to oscillate in the pre-somitic mesoderm, they are expressed within the pre-somitic mesoderm during somitogenesis. When the notochord is ablated during somitogenesis in the chick embryo, the proper number of somites forms, but the segmentation clock is delayed for the posterior two-thirds of the somites. The anterior somites are not affected. In one study, this phenotype was mimicked by Shh inhibitors, and timely somite formation was rescued by exogenous Shh protein, showing that the missing signal produced by the notochord is mediated by Shh. Signaling in separation and epithelialization of somites The physical separation of somites depends on the pulling of cells away from each other and the formation of borders and new adhesions between different cells. Studies indicate the importance of pathways involving Eph receptor and the Ephrin family of proteins, which coordinate border formation, in this process. Also, fibronectins and cadherins help the appropriate cells localize with each other. Specification and differentiation Regarding the paraxial mesoderm from which somites form, fate mapping experiments at the blastula stage show pre-somitic mesoderm progenitors at the site of gastrulation, referred to as the primitive streak in some organisms, in regions flanking the organizer. Transplant experiments show that only at the late gastrula stage are these cells committed