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

Mihailo Mirkovic, Leonardo G. Guilgur*, Alexandra Tavares, Diogo Passagem-Santos, Raquel A. Oliveira

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

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.

Original languageEnglish
Article numbere3000016
JournalPLoS Biology
Volume17
Issue number2
DOIs
Publication statusPublished - Feb 2019
Externally publishedYes

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