Mouse SAS-6 is required for centriole formation in embryos and integrity in embryonic stem cells

Abstract

Cell division fidelity is crucial for stem cell propagation and the maintenance of pluripotency. Centrosomes, which organize the mitotic spindle microtubules to ensure proper bipolar cell division, have a core of a pair of centrioles that duplicate once per cell cycle. At the onset of centriole biogenesis, SAS-6 forms a cartwheel structure, which is the precursor for the forming procentrioles. SAS-6 is essential for centriole formation in human cell lines and other organisms. However, the functions of SAS-6 in mouse stem cells remain to be elucidated. Here, we report that Sas-6-null mouse embryos lack centrioles, activate the mitotic surveillance cell death pathway and arrest at mid-gestation. In contrast, SAS-6 is not strictly required for centriole formation in mouse embryonic stem cells (mESCs) in vitro, but is still important to regulate centriole length, symmetry and ability to template cilia. Remarkably, centrioles appeared after just one day of culture of Sas-6-null blastocysts, from which mESCs are normally derived. Finally, the number of cells with centrosomes is drastically decreased upon the exit from a pluripotent state. Collectively, our data suggest a differential requirement for mouse SAS-6 in centriole formation or integrity depending on the cellular context, and highlight the robustness of mESCs in using SAS-6-independent centriole-duplication pathways.