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bioRxiv · 10.1101/2025.10.12.681824

Cell cycle oscillations in a polarity network facilitate state switching by morphogenetic cues

Ng, K.·Sebaa, H.·Hirani, N.·Chizh, A.·Messi, Z.·Bland, T.·Sugioka, K.·Goehring, N. W.
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Abstract

The proper establishment of cell form, fate, and function during morphogenesis requires precise 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 C. elegans germline blastomeres resolve this trade-off by creating a time-varying polarization landscape. Specifically, coupling the PAR polarity network to the cell-cycle kinase CDK-1 ensures that newborn cells operate in a low-feedback regime that lowers barriers to polarity state switching, allowing spatial cues to induce and orient PAR protein asymmetries. As CDK-1 activity rises at mitotic entry, increasing molecular feedback reinforces cue-induced asymmetries to yield robust and stable patterning of PAR domains. Consistent with this model, optogenetic and chemical perturbations show that low-CDK/low-feedback regimes destabilize PAR domains but are required for both de novo polarization and the reorientation of polarity in response to inductive cues. We propose that mitotic oscillations in cell polarity circuits dynamically optimize the polarization landscape to enable coordination of polarity with morphogenesis. Such temporal control of developmental networks is likely a general mechanism to balance robustness of cellular states with sensitivity to signal-induced state switching. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/681824v1_ufig1.gif" ALT="Figure 1"> View larger version (58K): org.highwire.dtl.DTLVardef@18b39f3org.highwire.dtl.DTLVardef@1898670org.highwire.dtl.DTLVardef@1d95517org.highwire.dtl.DTLVardef@1615f14_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Ng, K., Sebaa, H., Hirani, N., Chizh, A., Messi, Z., Bland, T., Sugioka, K., Goehring, N. W.. 2025-10-13. Cell cycle oscillations in a polarity network facilitate state switching by morphogenetic cues. https://doi.org/10.1101/2025.10.12.681824

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