Carl-Philipp Heisenberg (ISTA)

From embryo geometry to zygotic genome activation

Host: Erez Raz

Embryo geometry is among the most invariable traits of a species, suggesting that it may serve as a foundational principle to achieve developmental reproducibility and robustness. We show that the zebrafish zygote geometry causes early embryonic cleavages to occur asymmetrically and in a patterned manner, thereby generating a gradient of cell volume along the animal pole (AP)-margin axis in the embryo. This gradient impacts subsequent embryonic development in two important ways: First, through its impact on the nucleocytoplasmic ratio (N:C), it organizes cell divisions along mitotic phase waves originating near the AP and propagating toward the margin, with the division timing of each cell being determined by its N:C. Second, and more remarkably, the cell volume gradient patterns the onset of zygotic transcription hours later, at the midblastula transition, such that it is initiated first and sustained longer in the smaller, marginal blastoderm cells. This produces an asymmetry in zygotic gene expression along the AP-margin axis, thereby likely defining a previously unknown axis of cell fate specification in the embryo. Thus, our study reveals a novel symmetry-breaking role of the early embryo geometry in cell cycle and zygotic transcription patterning, establishing the blueprint for further embryonic development.

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