Perturbation of Rac1 signaling alters segmentation clock dynamics and somite size

The presomitic mesoderm is a transient embryonic tissue patterned along the anterior-posterior axis of vertebrates that periodically generates somites at its anterior end. Somitogenesis is driven by waves of gene expression that propagate from the posterior to the anterior end of the presomitic mesoderm under the control of the segmentation clock, a molecular oscillator. Using a mouse primary culture system, we performed a small-scale chemical screen targeting pathways implicated in cellular mechanics and we identified Rac1-dependent signaling as a modulator of segmentation clock dynamics. Pharmacological perturbation of Rac1 signaling reproducibly slowed oscillatory dynamics without disrupting intercellular synchrony. These changes were reversible and associated with increased somite length and reduced somite number. In addition, inhibition of Rac1 signaling was associated with changes in the expression of selected Wnt and Notch target genes in tail explants. These findings identify Rac1-dependent signaling as a candidate modulator of segmentation clock dynamics and somite morphogenesis, linking mechanical and molecular aspects of segmentation dynamics.