Fig. 5. Putative mechanism for the Tbx6-mediated regulation of Mesp genes. (A) Tbx6 activates Mesp2 expression through multiple Tbx6 binding sites. Notch signaling (NICD, red ovals) activates Mesp2 expression via factor X (gray ovals), which recognizes two neighboring Tbx6 binding sites in P2PSME. (Left) Schematic description of the Tbx6-dependent activation of Mesp2. (Middle column) lacZ expression in the P2Ewt transgenic embryo. (Right) Normal skeletal formation in the heterozygous fetus of a P2EmB1D mouse. (B) Mutation in Site B results in decreased expression of Mesp2. (C) A single Tbx6 binding site is unable to activate Mesp2 expression, presumably owing to an inability to respond to Notch signaling.