Mouse SAS-6 is required for centriole formation in embryos and integrity in embryonic stem cells
SAS-6 (SASS6) is essential for centriole formation in human cells and other organisms but its functions in the mouse are 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...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2024-02-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/94694 |
| _version_ | 1827325031532724224 |
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| author | Marta Grzonka Hisham Bazzi |
| author_facet | Marta Grzonka Hisham Bazzi |
| author_sort | Marta Grzonka |
| collection | DOAJ |
| description | SAS-6 (SASS6) is essential for centriole formation in human cells and other organisms but its functions in the mouse are 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 a SAS-6-independent centriole-biogenesis pathway. Collectively, our data suggest a differential requirement for mouse SAS-6 in centriole formation or integrity depending on PLK4 activity and centrosome composition. |
| first_indexed | 2024-03-07T14:15:20Z |
| format | Article |
| id | doaj.art-28dd9a25eb8b46eba2f3f01b76b849a1 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-03-07T14:15:20Z |
| publishDate | 2024-02-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
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| spelling | doaj.art-28dd9a25eb8b46eba2f3f01b76b849a12024-03-06T12:56:28ZengeLife Sciences Publications LtdeLife2050-084X2024-02-011310.7554/eLife.94694Mouse SAS-6 is required for centriole formation in embryos and integrity in embryonic stem cellsMarta Grzonka0https://orcid.org/0000-0003-3389-4816Hisham Bazzi1https://orcid.org/0000-0001-8388-4005Department of Cell Biology of the Skin and Department of Dermatology and Venereology, Medical Faculty, University of Cologne, Cologne, Germany; The Cologne Cluster of Excellence in Cellular Stress Responses in Aging-associated Diseases (CECAD), Medical Faculty, University of Cologne, Cologne, Germany; Graduate School for Biological Sciences, University of Cologne, Cologne, GermanyDepartment of Cell Biology of the Skin and Department of Dermatology and Venereology, Medical Faculty, University of Cologne, Cologne, Germany; The Cologne Cluster of Excellence in Cellular Stress Responses in Aging-associated Diseases (CECAD), Medical Faculty, University of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), Medical Faculty, University of Cologne, Cologne, GermanySAS-6 (SASS6) is essential for centriole formation in human cells and other organisms but its functions in the mouse are 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 a SAS-6-independent centriole-biogenesis pathway. Collectively, our data suggest a differential requirement for mouse SAS-6 in centriole formation or integrity depending on PLK4 activity and centrosome composition.https://elifesciences.org/articles/94694centrosomemESCsblastocystdifferentiationp5353BP1 |
| spellingShingle | Marta Grzonka Hisham Bazzi Mouse SAS-6 is required for centriole formation in embryos and integrity in embryonic stem cells eLife centrosome mESCs blastocyst differentiation p53 53BP1 |
| title | Mouse SAS-6 is required for centriole formation in embryos and integrity in embryonic stem cells |
| title_full | Mouse SAS-6 is required for centriole formation in embryos and integrity in embryonic stem cells |
| title_fullStr | Mouse SAS-6 is required for centriole formation in embryos and integrity in embryonic stem cells |
| title_full_unstemmed | Mouse SAS-6 is required for centriole formation in embryos and integrity in embryonic stem cells |
| title_short | Mouse SAS-6 is required for centriole formation in embryos and integrity in embryonic stem cells |
| title_sort | mouse sas 6 is required for centriole formation in embryos and integrity in embryonic stem cells |
| topic | centrosome mESCs blastocyst differentiation p53 53BP1 |
| url | https://elifesciences.org/articles/94694 |
| work_keys_str_mv | AT martagrzonka mousesas6isrequiredforcentrioleformationinembryosandintegrityinembryonicstemcells AT hishambazzi mousesas6isrequiredforcentrioleformationinembryosandintegrityinembryonicstemcells |