ArticleThe EMBO journal2021
Centrosome defects cause microcephaly by activating the 53BP1-USP28-TP53 mitotic surveillance pathway.
Article in The EMBO journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed.
- Low kinetochore-microtubule occupancy leaves a mitotic memory by delaying checkpoint silencing.Nature communications · 2026Article
- Mechanical constraints regulate embryonic stem cell mitosis in the developing brain.The EMBO journal · 2026Article
- KIF14 silencing suppresses cell proliferation and enhances chemosensitivity by modulating 53BP1 nucleocytoplasmic shuttling in non-WNT/non-SHH medulloblastoma.Cell death discovery · 2026Article
- Rare genetic causes of primary microcephaly in two Saudi families identified via whole-exome sequencing: Genomic and phenotypic delineation of pathogenicMolecular genetics and metabolism reports · 2026Article
- Insights into KIF11 pathogenesis in microcephaly-lymphedema-chorioretinopathy syndrome from a lymphatic perspective.JCI insight · 2026Article
- Biological clocks keep a watch on mitosis.Nature cell biology · 2026Review
- Cancer-associated USP28 missense mutations disrupt 53BP1 interaction and p53 stabilization.Nature communications · 2025Article
- DNA replication fork speed acts as a pacer in cortical neurogenesis.Nature communications · 2025Article
- PLK4: Master Regulator of Centriole Duplication and Its Therapeutic Potential.Cytoskeleton (Hoboken, N.J.) · 2025Review
- Generation of Neural Organoids and Their Application in Disease Modeling and Regenerative Medicine.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Meiotic divisions and round spermatid formation do not require centriole duplication in mice.PLoS genetics · 2025Article
- Developmental and tissue-specific roles of mammalian centrosomes.The FEBS journal · 2025Review
- Altered tubulin detyrosination due to SVBP malfunction induces cytokinesis failure and senescence, underlying a complex hereditary spastic paraplegia.Aging cell · 2025Article
- Roles of Cep215/Cdk5rap2 in establishing testicular architecture for mouse male germ cell development.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Centrioles are frequently amplified in early B cell development but dispensable for humoral immunity.Nature communications · 2024Article
- Spermatocytes have the capacity to segregate chromosomes despite centriole duplication failure.EMBO reports · 2024Article
- Mcph1, mutated in primary microcephaly, is also crucial for erythropoiesis.EMBO reports · 2024Article
- Control of cell proliferation by memories of mitosis.Science (New York, N.Y.) · 2024Article
- Regulation of p53 by the mitotic surveillance/stopwatch pathway: implications in neurodevelopment and cancer.Frontiers in cell and developmental biology · 2024Review
- Cep120 is essential for kidney stromal progenitor cell growth and differentiation.EMBO reports · 2024Article
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Mutations in centrosome genes deplete neural progenitor cells (NPCs) during brain development, causing microcephaly. While NPC attrition is linked to TP53-mediated cell death in several microcephaly models, how TP53 is activated remains unclear. In cultured cells, mitotic delays resulting from centrosome loss prevent the growth of unfit daughter cells by activating a pathway involving 53BP1, USP28, and TP53, termed the mitotic surveillance pathway. Whether this pathway is active in the developing brain is unknown. Here, we show that the depletion of centrosome proteins in NPCs prolongs mitosis and increases TP53-mediated apoptosis. Cell death after a delayed mitosis was rescued by inactivation of the mitotic surveillance pathway. Moreover, 53BP1 or USP28 deletion restored NPC proliferation and brain size without correcting the upstream centrosome defects or extended mitosis. By contrast, microcephaly caused by the loss of the non-centrosomal protein SMC5 is also TP53-dependent but is not rescued by loss of 53BP1 or USP28. Thus, we propose that mutations in centrosome genes cause microcephaly by delaying mitosis and pathologically activating the mitotic surveillance pathway in the developing brain.
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