TY - JOUR
T1 - Induced aneuploidy in neural stem cells triggers a delayed stress response and impairs adult life span in flies
AU - Mirkovic, Mihailo
AU - Guilgur, Leonardo G.
AU - Tavares, Alexandra
AU - Passagem-Santos, Diogo
AU - Oliveira, Raquel A.
N1 - Funding Information:
MM was supported by a Fundação para a Ciência e Tecnologia (FCT) fellowship (SFRH /BD/ 52438/2013). This work was supported by the following grants awarded to RAO: FCT Investigator grant (IF/00851/2012/CP0185/CT0004), EMBO Installation Grant (IG2778), and European Research Council Starting Grant (ERC-2014-STG-638917). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Funding Information:
Funding:MMwassupportedbyaFundac ¸ãoparaa CiênciaeTecnologia(FCT)fellowship(SFRH/BD/ 52438/2013).Thisworkwassupportedbythe followinggrantsawardedtoRAO:FCTInvestigator grant(IF/00851/2012/CP0185/CT0004),EMBO InstallationGrant(IG2778),andEuropean ResearchCouncilStartingGrant(ERC-2014-STG-638917).Thefundershadnoroleinstudydesign,
Publisher Copyright:
© 2019 Mirkovic et al.
PY - 2019/2
Y1 - 2019/2
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85062587888&partnerID=8YFLogxK
U2 - 10.1371/journal.pbio.3000016
DO - 10.1371/journal.pbio.3000016
M3 - Article
C2 - 30794535
SN - 1544-9173
VL - 17
JO - PLoS Biology
JF - PLoS Biology
IS - 2
M1 - e3000016
ER -