During early development, waves of gene activity sweep through the presomitic mesoderm, a temporary strip of embryonic tissue that is progressively divided into somites — paired blocks of cells that later form vertebrae, skeletal muscle and part of the skin. Each wave helps trigger the formation of a new pair of somites. In mice, a new pair of somites forms roughly every two hours, paced by an internal molecular clock called the segmentation clock.

After screening a collection of compounds that perturb cell mechanics and signalling, Charisios Tsiairis and Maria Pappa, his former PhD student, identified Rac1 as an unexpected regulator of the segmentation clock. Rac1 is a signaling protein usually linked to cell shape, movement and the cytoskeleton. Using cultured mouse embryonic tissue, the team found that disrupting Rac1 signaling slowed the segmentation clock without preventing cells from remaining synchronized.

The perturbation also changed the developmental output of the clock. Treated tissue formed fewer somites, but each somite was longer, while the overall length of the tissue remained similar. The researchers also detected changes in selected genes controlled by the Notch and Wnt pathways, which are central components of the segmentation system.

“The findings suggest that developmental timing is closely connected to the pathways that control how cells move, change shape and interact with their surroundings,” Tsiairis says. “They highlight an unexpected link between cell mechanics and the molecular clock that patterns the vertebrate body”.

The work may also help researchers understand developmental disorders that affect the spine, he adds. Defects in somite formation can contribute to congenital vertebral malformations, including abnormalities associated with the VACTERL spectrum, a group of conditions that affects several organs. “Understanding how cell behavior influences the segmentation clock could provide insight into the mechanisms underlying some of these conditions.”