Biology subjects

Sonnen, I.

Publications and source records attributed to Sonnen, I..

3 recordsLinked to original sources

bioRxiv2025

Spatiotemporal proteomics reveals dynamic antagonistic gradients shaping signalling waves

Embryonic development is driven by dynamic protein networks, yet how these dynamics shape morphogenesis remains incompletely understood. Somitogenesis, the rhythmic segmentation of vertebrate embryos, is governed by signalling gradients and oscillations in the presomitic mesoderm (PSM)1,2, but the corresponding protein dynamics are largely unknown. Perturbations in this process cause congenital spine disorders and can result in embryonic lethality3. Here, we introduce an integrated proteomics and microfluidics approach to resolve spatiotemporal protein expression in the developing mouse tail. To this end, we established a microfluidic system to synchronize oscillations in embryo tails grown in 3D, which we combined with mass-spectrometry and RNA sequencing. We uncover novel oscillatory proteins and differentially expressed genes along the anteroposterior axis. Building on this dataset, we identify a previously unrecognized antagonistic, dynamic ligand-receptor expression pattern in R-Spondin/LGR signalling explaining how Wnt-oscillation amplitude increases despite decreasing ligand levels in anterior PSM. Dynamic ligand expression was validated in mouse gastruloids. Perturbation of ligand dynamics reduced oscillation amplitude and impaired somite formation. Our study reveals a novel regulatory strategy in which dynamic antagonistic gradients fine-tune signalling strength, providing new mechanistic insight into how protein dynamics control tissue patterning. We anticipate our dataset to serve as foundation for mechanistic investigations of mammalian somitogenesis including the role of mechanics and metabolism. More broadly, our approach combining microfluidics-based synchronization of signalling in multicellular systems with omics analyses can be applied to study dynamics in other contexts such as in tissue homeostasis4 and regeneration5.

developmental biology↗

bioRxiv2025

Scaling of mouse somitogenesis by coupling of cell cycle to segmentation clock oscillations

While scaling developmental processes is fundamental to maintaining robust tissue patterning, the mechanisms underlying this process are enigmatic. Somitogenesis, the periodic segmentation of growing mesodermal tissue in vertebrate embryos1, involves precise scaling with the unsegmented presomitic mesoderm (PSM) over developmental time and under perturbation2-4. Somitogenesis is spatiotemporally regulated by FGF and Wnt morphogen gradients and the segmentation clock -- oscillations in Notch, Wnt, and FGF signalling5-7. Here, we find that cell proliferation is distributed throughout the oscillating PSM. Long-term single-cell tracking in mouse embryo tails uncovered a correlation between cell cycle progression and the segmentation clock, with microfluidics-based entrainment indicating coupling between the cell cycle and signalling oscillations, likely through S-phase inducing Cyclins. A theoretical model suggests this coupling ensures uniform PSM growth, uniform morphogen dilution and precise somite formation, which we validated experimentally by blocking cell proliferation. Our findings reveal that coupling cell proliferation to signalling oscillations is crucial for robust somitogenesis and precise somite scaling.

developmental biology↗

bioRxiv2021

Arnold tongue entrainment reveals dynamicalprinciples of the embryonic segmentation clock

Living systems exhibit an unmatched complexity, due to countless, entangled interactions across scales. Here we aim to understand a complex system, i.e. segmentation timing in mouse embryos, without a reference to these detailed interactions. To this end, we develop a coarse-grained approach, in which theory guides the experimental identification of the segmentation clock entrainment responses. We demonstrate period- and phase-locking of the segmentation clock across a wide range of entrainment parameters, including higher-order coupling. These quantifications allow to derive the phase response curve (PRC) and Arnold tongues of the segmentation clock, revealing its essential dynamical properties. Our results indicate that the somite segmentation clock has characteristics reminiscent of a highly non-linear oscillator close to an infinite period bifurcation and suggests the presence of long-term feedbacks. Combined, this coarse-grained theoretical-experimental approach reveals how we can derive simple, essential features of a highly complex dynamical system, providing precise experimental control over the pace and rhythm of the somite segmentation clock.

developmental biology↗