ArticleNature communications2019
Robust elimination of genome-damaged cells safeguards against brain somatic aneuploidy following Knl1 deletion.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 51 citations in OpenAlex.
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- Mechanical constraints regulate embryonic stem cell mitosis in the developing brain.The EMBO journal · 2026Article
- Microcephaly-associated genes asp and Sas4 influence chromatin organization and nuclear lamina structure in Drosophila melanogaster.Development (Cambridge, England) · 2026Article
- DNA replication fork speed acts as a pacer in cortical neurogenesis.Nature communications · 2025Article
- Propagation of neuronal micronuclei regulates microglial characteristics.Nature neuroscience · 2025Article
- A human-specific, concerted repression of microcephaly genes contributes to radiation-induced growth defects in cortical organoids.iScience · 2025Article
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- Developmental signals control chromosome segregation fidelity during pluripotency and neurogenesis by modulating replicative stress.Nature communications · 2024Article
- Aneuploidy is Linked to Neurological Phenotypes Through Oxidative Stress.Journal of molecular neuroscience : MN · 2024Article
- Permission to pass: on the role of p53 as a gatekeeper for aneuploidy.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2023Review
- Mitogen-induced defective mitosis transforms neural progenitor cells.Neuro-oncology · 2023Article
- The exon junction complex component EIF4A3 is essential for mouse and human cortical progenitor mitosis and neurogenesis.Development (Cambridge, England) · 2023Article
- Why Don't the Mutant Cells That Evade DNA Repair Cause Cancer More Frequently? Importance of the Innate Immune System in the Tumor Microenvironment.International journal of molecular sciences · 2023Review
- The Loss-Function ofSensors (Basel, Switzerland) · 2023Article
- Review
- An entosis-like process induces mitotic disruption in Pals1 microcephaly pathogenesis.Nature communications · 2023Article
- P53 independent pathogenic mechanisms contribute to BubR1 microcephaly.Frontiers in cell and developmental biology · 2023Article
- The impact of TP53 activation and apoptosis in primary hereditary microcephaly.Frontiers in neuroscience · 2023Review
- DNA damage and repair: underlying mechanisms leading to microcephaly.Frontiers in cell and developmental biology · 2023Review
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5 authors at 1 institution in 1 country.
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Abstract
The brain is a genomic mosaic shaped by cellular responses to genome damage. Here, we manipulate somatic genome stability by conditional Knl1 deletion from embryonic mouse brain. KNL1 mutations cause microcephaly and KNL1 mediates the spindle assembly checkpoint, a safeguard against chromosome missegregation and aneuploidy. We find that following Knl1 deletion, segregation errors in mitotic neural progenitor cells give rise to DNA damage on the missegregated chromosomes. This triggers rapid p53 activation and robust apoptotic and microglial phagocytic responses that extensively eliminate cells with somatic genome damage, thus causing microcephaly. By leaving only karyotypically normal progenitors to continue dividing, these mechanisms provide a second safeguard against brain somatic aneuploidy. Without Knl1 or p53-dependent safeguards, genome-damaged cells are not cleared, alleviating microcephaly, but paradoxically leading to total pre-weaning lethality. Thus, mitotic genome damage activates robust responses to eliminate somatic mutant cells, which if left unpurged, can impact brain and organismal fitness.
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