Mouse SAS‑6 is required for centriole formation in embryos and integrity in embryonic stem cells
Abstract
SAS‑6 (SASS6) is essential for centriole formation in human cells and other organisms but its function in mouse is unclear. Here, we report that Sass6‑mutant mouse embryos lack centrioles, activate the mitotic surveillance cell death pathway and arrest at mid‑gestation. In contrast, SAS‑6 is not required for centriole formation in mouse embryonic stem cells (mESCs), but is essential to maintain centriole architecture. Of note, centrioles appeared after just one day of culture of Sass6‑mutant blastocysts, from which mESCs are derived. Conversely, the number of cells with centrosomes is drastically decreased upon the exit from a mESC pluripotent state. At the mechanistic level, the activity of the master kinase in centriole formation, PLK4, associated with increased centriolar and centrosomal protein levels, endow mESCs with the robustness in using SAS‑6‑independent centriole-duplication pathways. Collectively, our data suggest a differential requirement for mouse SAS‑6 in centriole formation or integrity depending on PLK4 and centrosome composition.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files; source data files have been provided for Figures 2 and 3.
Article and author information
Author details
Funding
Deutsche Forschungsgemeinschaft (73111208 - SFB829)
- Hisham Bazzi
Deutsche Forschungsgemeinschaft (Project-ID 331249414 - BA 5810/1-1)
- Hisham Bazzi
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: The animal generation application (84-02.04.2014.A372), notifications and breeding applications (84-02.05.50.15.039, 84-02.04.2015.A405, UniKöln_Anzeige{section sign}4.20.026, 84-02.04.2018.A401, 81-02.04.2021.A130) were approved by the Landesamt für Natur, Umwelt, und Verbraucherschutz Nordrhein-Wesdalen (LANUV-NRW) in Germany.
Copyright
© 2024, Grzonka & Bazzi
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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