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Geometric, cell cycle and maternal-to-zygotic transition-associated YAP dynamics during preimplantation embryo
Madeleine Chalifoux1,2, Maria Avdeeva3, Eszter Posfai1
1Department of Molecular Biology, Princeton University, Princeton, New Jersey, USA.
Biorxiv : the Preprint Server for Biology
|March 10, 2025
Summary
Early mammalian embryo development involves cell fate decisions driven by the Hippo pathway and YAP. This study reveals how YAP levels change dynamically during cell division and positioning, influencing cell fate. Mechanical forces do not alter YAP localization.
Area of Science:
- Developmental Biology
- Cell Biology
- Genetics
Background:
- The first cell fate decision in mammalian embryos separates inner cell mass (ICM) and trophectoderm (TE) lineages.
- The Hippo signaling pathway and its effector YAP regulate lineage-specific gene expression.
- YAP's dynamic response to cellular changes during early embryogenesis is not fully understood.
Purpose of the Study:
- To investigate how YAP localization and levels change dynamically during early mammalian cell fate segregation.
- To understand the interplay between YAP, cell geometry, and cell cycle progression.
- To elucidate the mechanisms establishing YAP levels critical for ICM fate.
Main Methods:
- Quantitative live imaging of endogenously tagged YAP in mammalian embryos.
- Simultaneous monitoring of cellular geometric features and cell cycle progression.
- Application of a probabilistic model to analyze dynamic YAP and cell geometry data.
Main Results:
- YAP levels are influenced by maternally provided YAP, cell cycle, and post-division positioning delays.
- Establishing low nuclear YAP for ICM fate is largely driven by passive cell cycle mechanisms.
- Mechanical perturbations causing cell shape changes did not affect YAP localization in the embryo.
Conclusions:
- YAP levels are dynamically regulated by multiple factors during early embryonic cell fate decisions.
- Cell cycle-associated mechanisms play a significant role in setting YAP levels for ICM fate.
- This study provides insights into how developmental timing and cellular dynamics shape YAP's role in lineage specification.
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