CollectiveDynamics SIGNED

Project "CollectiveDynamics" data sheet

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 Project objective

In this proposal, we study collective signaling oscillations during embryonic patterning. Signaling oscillations during vertebrate embryo segmentation are governed by a molecular oscillatory machinery referred to as segmentation clock (Palmeirim et al., 1997). The segmentation clock is linked to periodic activity of the Notch, Wnt and Fgf pathway in presomitic mesoderm (PSM) cells (period~2 hours in mouse embryos). Importantly, PSM cells display complex, collective synchronization and, as a result, wave-like activity patterns (phase waves) sweep periodically along the embryonic axis. We have previously shown that phase waves are an emergent and collective phenomenon in PSM cells (Tsiairis and Aulehla, 2016). Conceptually, this proposal builds on our previous discovery that the relative timing between Wnt/Notch oscillations is critical for proper mesoderm patterning (Sonnen et al., 2018). What are the principles underlying the emergence of collective synchronization and how do PSM cells decode relative timing of signalling oscillations? As outlined in this proposal, we are now in a unique position to address these fundamental questions in novel ways. Importantly, we have established an entrainment strategy that enables, for the first time, precise experimental control of oscillation dynamics (Sonnen et al., 2018). Our strategy is to further expand the entrainment approach, including the future use of optogenetics, and also combine it with our expertise in quantitative, multi-scale analysis of signalling dynamics and functional, genetic perturbations. A central aim of this ERC proposal is to build on discoveries made in versatile in vitro assays that we developed and to address their significance in vivo. To this end, we propose a novel line of research using the medaka fish model. We will entrain and challenge collective synchronization in vivo to address how signalling oscillations are integrated with growth dynamics to yield robust embryonic patterning.