A cell-motility pathway helps set the pace of embryo development

Researchers at the Friedrich Miescher Institute for Biomedical Research have discovered that a cell-motility pathway plays a crucial role in regulating the pace of embryo development. The study, published in the journal Development, reveals that this molecular pathway, which controls cell shape and movement, also helps maintain the rhythm of the segmentation clock that organizes the formation of vertebrae and other tissues.

During early development, waves of gene activity create a temporary strip of embryonic tissue called the presomitic mesoderm, which is divided into somites—paired blocks of cells that eventually develop into vertebrae, skeletal muscle, and part of the skin. The segmentation clock, an internal molecular clock, controls the formation of new somite pairs roughly every two hours in mice.

In their research, Charisios Tsiairis and Maria Pappa identified Rac1, a signaling protein typically associated with cell shape, movement, and the cytoskeleton, as an unexpected regulator of the segmentation clock. By disrupting Rac1 signaling in cultured mouse embryonic tissue, the team found that the clock's oscillations slowed down, fewer somites were formed, and the somites became longer. However, cellular synchrony and overall tissue length remained unchanged.

The researchers also observed alterations in genes controlled by the Notch and Wnt pathways, which are essential components of the segmentation system. These findings suggest that the timing of developmental processes is closely connected to pathways controlling cell mechanics, shape changes, and interactions with the environment.

The results highlight an unexpected link between cell mechanics and the molecular clock that patterns the vertebrate body. Understanding how cell behavior influences the segmentation clock could provide valuable insights into the mechanisms behind congenital spinal malformations, such as those in the VACTERL spectrum, which affect multiple organs.