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Synchronised waves control embryo patterning
As a mouse embryo journeys from a single cell into a complex organism, countless processes affect its cellular pattern of development to ensure cells develop in exactly the right location and at the right time. The activation of specific genes during early development, results in continuous waves of cellular changes — including embryo body segmentation. Scientists at EMBL (European Molecular Biology Laboratory) can now explain how this rhythmic exchange, induced by waves of signals from the Wnt and Notch pathways, induces new embryonic segments to form.
The work was just published online February 22, 2018 in Cell magazine.
Formation of new body segments is also impacted by a molecular clock. However, the Wnt and Notch pathways send out two different, but periodic pulses of activity which happen to coincide with segment formation in an embryo. In their paper, scientists from the Aulehla and Merten labs at EMBL, reveal how the timing between these two waves creates that segmentation.
At a specific time, the Wnt and Notch waves get in sync and overlap, a step that coincides with formation of each new embryo segment.
To test what happened when the two waves were not in sync, the team developed a strategy to control the two unique pulses. Katharina Sonnen, an EMBL postdoctoral researcher working in both the Aulehla and Merten labs, was able to synchronise Wnt and Notch waves to an external rhythm. Strikingly, that synchronised wave was the only time a new segment would form. Changing the relative timing of either Wnt or Notch, prevented any segment formation.
"It's the first time that we've been able to directly test the importance of timing in developing systems. This shows that vital information for the development of an embryo is encoded in dynamic, oscillating signals. In the future, this approach could be used to test the importance of rhythm in other contexts - for example in stem cells and disease states, where the same signaling pathways are in place."
• Wnt and Notch signaling wave dynamics differ within segmenting mouse mesoderm
• Entraining oscillations by microfluidics allows external control of the dynamics
• Oscillatory Wnt and Notch signaling networks are coupled at the level of dynamics
• Relative timing of Wnt and Notch signaling oscillations is critical for segmentation
How signaling dynamics encode information is a central question in biology. During vertebrate development, dynamic Notch signaling oscillations control segmentation of the presomitic mesoderm (PSM). In mouse embryos, this molecular clock comprises signaling oscillations of several pathways, i.e., Notch, Wnt, and FGF signaling. Here, we directly address the role of the relative timing between Wnt and Notch signaling oscillations during PSM patterning. To this end, we developed a new experimental strategy using microfluidics-based entrainment that enables specific control of the rhythm of segmentation clock oscillations. Using this approach, we find that Wnt and Notch signaling are coupled at the level of their oscillation dynamics. Furthermore, we provide functional evidence that the oscillation phase shift between Wnt and Notch signaling is critical for PSM segmentation. Our work hence reveals that dynamic signaling, i.e., the relative timing between oscillatory signals, encodes essential information during multicellular development.
Authors: Katharina F. Sonnen, Volker M. Lauschke4, Julia Uraji, Henning J. Falk, Yvonne Petersen, Maja C. Funk, Mathias Beaupeux, Paul François, Christoph A. Merten, Alexander Aulehla
Similar research and publication: ES cell-derived presomitic mesoderm-like tissues for analysis of synchronized oscillations in the segmentation clock
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Oscillating signals sent through the Wnt and Notch pathways initiate segmentation in the embryo body plan. Image credit: Katharina Sonnen and Alexander Aulehla (EMBL) in CELL.