Induced aneuploidy in neural stem cells triggers a delayed stress response and impairs adult life span in flies.

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  • Additional Information
    • Source:
      Publisher: Public Library of Science Country of Publication: United States NLM ID: 101183755 Publication Model: eCollection Cited Medium: Internet ISSN: 1545-7885 (Electronic) Linking ISSN: 15449173 NLM ISO Abbreviation: PLoS Biol Subsets: MEDLINE
    • Publication Information:
      Original Publication: San Francisco, CA : Public Library of Science, [2003]-
    • Subject Terms:
      Aneuploidy* ; Stress, Physiological*; Drosophila melanogaster/*physiology ; Longevity/*physiology ; Neural Stem Cells/*physiology; Animals ; Brain/physiology ; Cell Cycle ; Cell Cycle Proteins/metabolism ; Cell Self Renewal ; Chromosomal Instability ; Chromosomal Proteins, Non-Histone/metabolism ; Chromosomes, Insect/metabolism ; Karyotype ; Kinetics ; Larva/physiology ; Mitosis ; Neural Stem Cells/cytology ; Time Factors ; Wings, Animal/physiology ; Cohesins
    • Abstract:
      Studying aneuploidy during organism development has strong limitations because chronic mitotic perturbations used to generate aneuploidy usually result in lethality. We developed a genetic tool to induce aneuploidy in an acute and time-controlled manner during Drosophila development. This is achieved by reversible depletion of cohesin, a key molecule controlling mitotic fidelity. Larvae challenged with aneuploidy hatch into adults with severe motor defects shortening their life span. Neural stem cells, despite being aneuploid, display a delayed stress response and continue proliferating, resulting in the rapid appearance of chromosomal instability, a complex array of karyotypes, and cellular abnormalities. Notably, when other brain-cell lineages are forced to self-renew, aneuploidy-associated stress response is significantly delayed. Protecting only the developing brain from induced aneuploidy is sufficient to rescue motor defects and adult life span, suggesting that neural tissue is the most ill-equipped to deal with developmental aneuploidy.
      Competing Interests: The authors have declared that no competing interests exist.
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    • Accession Number:
      0 (Cell Cycle Proteins)
      0 (Chromosomal Proteins, Non-Histone)
    • Publication Date:
      Date Created: 20190223 Date Completed: 20191105 Latest Revision: 20231213
    • Publication Date:
      20240104
    • Accession Number:
      PMC6402706
    • Accession Number:
      10.1371/journal.pbio.3000016
    • Accession Number:
      30794535