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Manipulation of Ploidy in Caenorhabditis elegans
Published on: March 15, 2018
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Tetraploidy causes chromosomal instability in acentriolar mouse embryos
Lia Mara Gomes Paim1, Greg FitzHarris2,3
1Centre de Recherche du Centre Hospitalier de l'Université de Montréal, H2X 0A9, Montreal, QC, Canada.
Nature Communications
|October 25, 2019
Summary
Tetraploidisation can cause chromosomal instability (CIN) in cancer cells through altered microtubule dynamics, not just multipolar spindles. This leads to chromosome segregation errors and aneuploidies in tetraploid cells.
Area of Science:
- Cell Biology
- Genetics
- Cancer Research
Background:
- Tetraploidisation is a common event in cancer evolution.
- The prevailing model suggests tetraploidy drives chromosomal instability (CIN) via multipolar spindle formation due to centriole duplication.
Purpose of the Study:
- To investigate the mechanism by which tetraploidy induces CIN in mammalian cells.
- To explore alternative pathways driving CIN beyond centriole duplication and multipolar spindles.
Main Methods:
- Utilizing mouse blastomeres, which lack centrioles initially, to study tetraploidy's effects.
- Analyzing spindle formation, microtubule dynamics, and chromosome segregation in tetraploid cells.
Main Results:
- Tetraploid blastomeres form bipolar spindles, with multipolar spindles being rare.
- Altered kinetochore-microtubule turnover leads to attachment defects and chromosome segregation errors.
- Tetraploid cells exhibit increased CIN and whole chromosome aneuploidies.
Conclusions:
- Tetraploidy drives CIN through a novel mechanism involving altered microtubule dynamics and chromosome segregation errors.
- This pathway is independent of the canonical model involving multipolar spindle formation.
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