Mechanical Regulation of the Segmentation Clock

Feyza Nur Arslan

Oscillatory biochemical signals are increasingly recognized as fundamental mechanisms for encoding dynamic information in biological systems. A compelling example of such processes is vertebrate body axis segmentation, where expression waves of a molecular oscillator known as the segmentation clock sweep across the presomitic mesoderm (PSM), governing periodic formation of segments. While there is evidence of spatiotemporal variations in cell and tissue mechanics across the PSM, the extent to which mechanical properties and oscillatory signaling are interdependent remains poorly understood. Here, we investigate the interplay between tissue mechanics and segmentation clock dynamics using the zebrafish embryo as a model system. Through the combination of in vivo whole-mount live imaging of transgenic embryos marking the segmentation clock and cell cytoskeleton, immunostainings, and morphometric analysis at single-cell resolution, we discovered a cell shape and contractility gradient across the PSM as clock oscillations slow down. Chemical perturbation of contractility not only altered cell shape and motility but also impacted the periodicity of the segmentation clock. In line with this, experiments in primary PSM single-cell cultures revealed that contractility markers change in a cell-autonomous manner during segmentation clock oscillations, and that pharmacological disruption of the cytoskeleton perturbs clock dynamics, mirroring in vivo observations. Collectively, our preliminary findings suggest a coordinated interplay between segmentation clock oscillations and cellular mechanics, highlighting a potential coupling of oscillatory signaling and morphogenesis.