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Spatially ordered zygotic genome activation fulfills embryo quality control.

Created on 08 Sep 2026

Authors

Wenchao Qian, Hui Chen, Hongju Lee, Matthew C Good

Published in

The Journal of cell biology. Volume 225. Issue 10. Oct 05, 2026. Epub Sep 08, 2026.

Abstract

Early embryo development features autonomous, maternally driven cell divisions that self-organize the multicellular blastula or blastocyst tissue. Maternal control cedes to the zygote starting with the onset of widespread zygotic genome activation (ZGA), which is essential for subsequent cell fate determination and morphogenesis. Intriguingly, although ZGA onset is highly regulated at the level of the whole embryo, it can be non-homogenous and precisely patterned at the single-cell level. We previously demonstrated a stereotyped spatial and temporal ordering of ZGA in a model vertebrate embryo. Unknown, however, was whether this precise ZGA patterning was required for development. To address this fundamental question, we devised a strategy to spatially control cell divisions that perturb blastula embryo organization. We demonstrate the feasibility of spatially inverting the cell size pattern of embryos and find that these inverted embryos exhibit a flipped pattern of ZGA. Mispatterned ZGA along the animal-vegetal axis triggers embryo apoptosis, revealing that gastrula embryos have a built-in quality control system to sense inappropriate ZGA patterning, including regionalized defects in transcriptional onset. The quality control response is nonautonomous, dependent on an anti-apoptotic signal that suppresses cell death outside the animal hemisphere. These results reveal the requirement of properly patterned ZGA for normal development and the existence of a surveillance system of embryo quality control exquisitely tuned to the spatial and temporal ordering of genome activation and zygotic gene expression.

PMID:
42708802
Bibliographic data and abstract were imported from PubMed on 08 Sep 2026.

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