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Peer-reviewedCC BY 4.0Nature Communications

Spatiotemporal proteomics reveals dynamic antiparallel gradients shaping signalling waves

2 more authors

Abstract

Embryonic development is driven by dynamic protein networks, yet how these dynamics shape morphogenesis remains poorly understood. 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 synchronisation of mouse embryo tails with quantitative proteomics and transcriptomics to resolve spatiotemporal protein dynamics during somitogenesis. We identify proteins with dynamic expression during 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 is validated in mouse gastruloids, and perturbation of ligand dynamics reduces oscillation amplitude and impairs 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.

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BibTeX
@article{meijer2026spatiotemporal,
  title = {{Spatiotemporal proteomics reveals dynamic antiparallel gradients shaping signalling waves}},
  author = {Wilke H. M. Meijer and Virginia Andrade and Suzan Stelloo and Wouter M. Thomas and Marek J. van Oostrom and Balaji Srinivasan and Dimitri Fabreges and Sita Venkataraman and Sonja D. C. Weterings and Jan-Daniël de Leede-Scheven and Eveline F. Ilcken and Kim T. J. Peters and Michiel Vermeulen and Katharina F. Sonnen},
  journal = {Nature Communications},
  year = {2026},
  month = oct,
  doi = {10.1038/s41467-026-78911-0},
  url = {https://www.nature.com/articles/s41467-026-78911-0},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Spatiotemporal proteomics reveals dynamic antiparallel gradients shaping signalling waves
AU  - Wilke H. M. Meijer
AU  - Virginia Andrade
AU  - Suzan Stelloo
AU  - Wouter M. Thomas
AU  - Marek J. van Oostrom
AU  - Balaji Srinivasan
AU  - Dimitri Fabreges
AU  - Sita Venkataraman
AU  - Sonja D. C. Weterings
AU  - Jan-Daniël de Leede-Scheven
AU  - Eveline F. Ilcken
AU  - Kim T. J. Peters
AU  - Michiel Vermeulen
AU  - Katharina F. Sonnen
PY  - 2026
DA  - 2026/10/25
JO  - Nature Communications
DO  - 10.1038/s41467-026-78911-0
UR  - https://www.nature.com/articles/s41467-026-78911-0
AB  - Embryonic development is driven by dynamic protein networks, yet how these dynamics shape morphogenesis remains poorly understood. 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 synchronisation of mouse embryo tails with quantitative proteomics and transcriptomics to resolve spatiotemporal protein dynamics during somitogenesis. We identify proteins with dynamic expression during 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 is validated in mouse gastruloids, and perturbation of ligand dynamics reduces oscillation amplitude and impairs 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.
SN  - 2041-1723
ER  -