<i>Fgf4</i> maintains <i>Hes7</i> levels critical for normal somite segmentation clock function.

Abstract

During vertebrate development, the presomitic mesoderm (PSM) periodically segments 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 <i>Fgf4</i> or <i>Fgf8</i>, which we previously demonstrated act redundantly to prevent PSM differentiation. <i>Fgf8</i> is not required for somitogenesis, but <i>Fgf4</i> mutants display a range of vertebral defects. We analyzed <i>Fgf4</i> mutants by quantifying mRNAs fluorescently labeled by hybridization chain reaction within Imaris-based volumetric tissue subsets. These data indicate that FGF4 maintains <i>Hes7</i> levels and normal oscillatory patterns. To support our hypothesis that FGF4 regulates somitogenesis through <i>Hes7</i>, we demonstrate genetic synergy between <i>Hes7</i> and <i>Fgf4</i>, but not with <i>Fgf8</i>. Our data indicate that <i>Fgf4</i> is potentially important in a spectrum of human Segmentation Defects of the Vertebrae caused by defective Notch oscillations.