Fgf4 is critical for maintaining Hes7 levels and Notch oscillations in the somite segmentation clock

During vertebrate development, the presomitic mesoderm (PSM) is periodically segmented into somites, which will form the segmented vertebral column and associated muscle, connective tissue, and dermis. The periodicity of somitogenesis is regulated by a segmentation clock of oscillating Notch activity. Here, we examined mouse mutants lacking only or , which we previously demonstrated act redundantly to prevent PSM differentiation. is not required for somitogenesis, but mutants display a range of vertebral defects. We analyzed mutants by quantifying mRNAs fluorescently labeled by hybridization chain reaction within Imaris-based volumetric tissue subsets. These data indicate that FGF4 controls Notch pathway oscillations through the transcriptional repressor, HES7. This hypothesis is supported by demonstrating a genetic synergy between and , but not with . Thus, is an essential Notch oscillation regulator and potentially important in a spectrum of human Segmentation Defects of the Vertebrae caused by defective Notch oscillations.