PT  - JOURNAL ARTICLE
AU  - Mishra, Nikhil
AU  - Li, Yuting I.
AU  - Hannezo, Edouard
AU  - Heisenberg, Carl-Philipp
TI  - Geometry-driven asymmetric cell divisions pattern cell cycles and zygotic genome activation in the zebrafish embryo
AID  - 10.1101/2025.02.03.636134
DP  - 2025 Jan 01
TA  - bioRxiv
PG  - 2025.02.03.636134
4099  - http://biorxiv.org/content/early/2025/02/03/2025.02.03.636134.short
4100  - http://biorxiv.org/content/early/2025/02/03/2025.02.03.636134.full
AB  - Synchrony in early embryonic cell cycles, followed by gradual desynchronization at the midblastula transition (MBT), is a widely conserved feature across animal phylogeny. Embryos that fail to maintain synchrony during these early stages do not develop properly, highlighting the critical importance of this process. However, the mechanisms underlying the initial synchronization and subsequent desynchronization of cell cycles - and their developmental significance - remain poorly understood. Here we show that the initial cell cycles in zebrafish embryos are synchronized primarily through cell-autonomous mechanisms. Furthermore, we reveal that their gradual desynchronization is spatially patterned by the geometry of the dividing embryo, which establishes a cell volume gradient through unequal cell divisions. This volume gradient translates into a cell cycle gradient by unequal S-phase lengthening due to volume-dependent changes in the nucleocytoplasmic ratio. Importantly, we find that this volume gradient, and the resulting cell cycle gradient, also spatiotemporally patterns the initiation of zygotic genome activation (ZGA) - a hallmark of MBT - within the embryo, thereby serving as a key symmetry-breaking event in animal development. Thus, our findings uncover a previously unrecognized role for early embryonic geometry in establishing an axis of transcriptional asymmetry during the transition to developmental autonomy.Competing Interest StatementThe authors have declared no competing interest.