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

PLoS Biology
Mihailo MirkovicRaquel A Oliveira

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.

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Citations

Jun 28, 2019·Cell Cycle·Rita BrásLuís Pedro Resende
Jun 3, 2020·Open Biology·Stephan U Gerlach, Héctor Herranz
Dec 10, 2019·Oxidative Medicine and Cellular Longevity·Marcelina KierońMichalina Wężyk
Mar 25, 2021·Cell Reports·Akshay NarkarRong Li
May 6, 2021·Biology Open·Rita BrásLuís Pedro Resende
Dec 10, 2021·PLoS Genetics·M Felicia Basilicata, Claudia Isabelle Keller Valsecchi

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Methods Mentioned

BETA
Fluorescence
Chromosomal aberrations
electrophoresis
Ubiquitination

Software Mentioned

GraphPad
Prism

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