Cell cycle oscillations in a polarity network facilitate state switching by morphogenetic cues More about Open Access at the Crick

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Kangbo Ng Hadjar Sebaa Nisha Hirani Alex Chizh Zeno Messi Tom Bland Kenji Sugioka Nathan Goehring

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Abstract

The establishment of cell form, fate, and function during morphogenesis requires coordination between cell polarity and developmental cues. To achieve this, cells must establish polarity domains that are stable yet sensitive to guiding cues. Here, we show that Caenorhabditis elegans germline blastomeres use a time-varying polarization landscape to resolve this trade-off. Specifically, coupling the PAR polarity network to the oscillatory activity of cell cycle kinase CDK-1 ensures that newborn cells operate in a low feedback regime that lowers barriers to state switching, allowing spatial cues to induce and orient PAR protein asymmetries. As CDK-1 activity rises during mitosis, molecular feedback increases, reinforcing cue-induced asymmetries to yield robust and stable patterning of PAR polarity domains. Consistent with this model, we show that low CDK/feedback regimes destabilize PAR domains but are required for de novo polarization and polarity reorientation by cues. We propose that oscillatory networks represent a general mechanism for dynamically optimizing cellular decision-making landscapes, ensuring robust, signal-induced state switching during development.