Spatiotemporal proteomics reveals dynamic antiparallel gradients shaping signalling waves [Spatiotemporal RNAseq]

Somitogenesis, the rhythmic segmentation of vertebrate embryos, is controlled by signalling gradients and oscillations in the presomitic mesoderm (PSM), but the underlying protein dynamics remain largely unknown. Here, we combine microfluidic synchronization of mouse embryo tails with quantitative proteomics and transcriptomics to resolve spatiotemporal protein dynamics during somitogenesis.

We identify dynamic proteins not previously linked to somitogenesis and reveal an antiparallel, dynamic R-Spondin/LGR signalling pattern that explains how Wnt oscillation amplitude increases despite declining Wnt ligand levels in the anterior PSM. Dynamic ligand expression was validated in mouse gastruloids, and perturbation of ligand dynamics reduced oscillation amplitude and impaired somite formation. Together, our findings identify R-Spondin as a dynamic amplifier of Wnt signalling oscillations and provide a mechanistic framework for understanding how protein dynamics regulate mammalian tissue patterning.