Fig. 7.

The CREB family forms a core segmentation module in somitogenesis. In our model depicted at Phase 3, CREB family activity (P-CREB) oscillation (in green) has critical roles in somitogenesis: to mediate Wnt3a signaling at the anterior end of its gradient (blue) in the P-CREB domain (green/blue hatched marks), coordinate the segmentation machinery in region II, and maintain somite epithelium. In WT (magnified, Middle), P-CREB (green area) directly regulates the expression of Dll-1 at S−2/S−1 and mediates the expression of Tbx6. In turn, Dll-1/Notch signaling and Tbx6 synergize to activate Mesp2 to define the anterior somite half (white band) of S−1. Tbx6 and Mesp2 subsequently activate Ripply2 to refine Mesp2 expression. The coordination of P-CREB and Mesp2 in region II drives the formation of somite boundaries and A/P patterning at S-1 and S0. Black dotted line marks the future somite boundary. (Bottom) In the CREB family mutant, there are reduced Dll-1/Notch signaling and Tbx6 expression, sustained albeit at a lower level of Mesp2 stripe, and loss of Ripply2, leading to anteriorized somites. Blue text represents Wnt-regulated genes. Light text represents reduced expression. Symbols in regulatory loop: arrow for direct activation, dotted arrow for indirect or unknown activation, T for inhibition, and X for lost regulatory pathway or gene expression. A, anterior somite half; P, posterior somite half.