Coupling of cell proliferation to the segmentation clock promotes robust somite scaling

How developing tissues coordinate growth and patterning to maintain their proportions remains unclear. During vertebrate somitogenesis, somite size scales with the presomitic mesoderm (PSM), where morphogen gradients and oscillating Notch, Wnt (wingless and Int-1), and fibroblast growth factor (FGF) signaling regulate segmentation. We find that proliferation is uniformly distributed throughout the oscillating PSM and, using long-term single-cell tracking and microfluidic entrainment in mouse embryo tails, provide evidence for functional coupling between cell-cycle progression and the segmentation clock, likely involving periodic cyclin D1 regulation among other mechanisms. A minimal model suggests that this coupling promotes uniform PSM growth and morphogen dilution, supporting robust somite formation. Loss of clock function increases Mesp2 patterning irregularity, whereas inhibiting proliferation alters morphogen profiles and somite scaling. Human in vitro somitogenesis models show a comparable clock-cell-cycle phase relationship, suggesting conservation across species. Together, these findings link clock-coupled proliferation to coordinated tissue growth, robust patterning, and scaling.