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Section of the tracheal dorsal trunk of a larva of Drosophila. Nuclei, in blue, cell membrane, in red, and ref(2)P, in yellow (Beatriz Pino-Jiménez).

Key mechanism in embryonic development revealed: pivotal role of DNA copy number

Led by Dr. Jordi Casanova and Dr. Panagiotis Giannios, a team of researchers at IRB Barcelona and IBMB-CSIC, based in the Barcelona Science Park, has revealed the relationship between autophagy and polyploidy, the latter a phenomenon in which cells contain multiple copies of genetic material. In this regard, they have discovered a scenario where the level of autophagy is much higher in cells with several copies of DNA and that it can even trigger this programmed cell death.

Published in the journal Autophagy, this finding sheds light on the biological processes that shape organisms during the early stages of life, and it paves the way to a better understanding of developmental diseases and also cancer.

“Polyploidy is a common phenomenon in many species, including humans, and understanding its implications for embryonic development could have a significant impact in medicine”, explains Dr. Casanova, head of the Development and Morphogenesis in Drosophila lab at IRB Barcelona.

Progenitor cells and polyploidy

Progenitor cells can give rise to different cell types. In the case of the Drosophila melanogaster fly, the animal model used in this study, the progenitor cells are larval cells that conserve the capacity to give rise to the adult organism. These cells do not present polyploidy (they have a single copy of the set of chromosomes) and this allows them to survive metamorphosis and form part of the adult.

“In the case of cancer, it is common for cells to have several copies of DNA (polyploidy), and this property might confer increased resistance, for example, to chemotherapy treatment. This is why it is important to understand this process,” adds Dr. Giannios, a postdoctoral researcher in the same laboratory.

Polyploidy in the trachea of the fruit fly

To study this process, the researchers worked with the trachea of the D. melanogaster fly as a model, which presents a variety of cells of the same type, some with polyploidy and others without.

“Working with the trachea of the Drosophila fly has allowed us to compare cells of the same type, some presenting polyploidy and others not, and to see how polyploidy correlates with cell death during metamorphosis”, explains Dr. Beatriz Pino-Jiménez, first author of the work, who carried out this project as part of her doctoral studies.The research team is now working to determine whether polyploid cells respond better to stress situations and, if so, what the mechanisms underlying this response are.

This work was funded by the Spanish Ministry of Science and Innovation and the Government of Catalonia.

» Reference article: “Polyploidy-associated autophagy promotes larval tracheal histolysis at Drosophila metamorphosis”. Beatriz Pino-Jiménez, Panagiotis Giannios & Jordi Casanova Autophagy (2022) DOI: 10.1080/15548627.2023.2231828

» Link to the news: IRB website [+]