Polyploidy in development and tumor models in Drosophila

Abstract

Polyploidy, a cell status defined as more than two sets of genomic DNA, is a conserved strategy across species that can increase cell size and biosynthetic production, but the functional aspects of polyploidy are nuanced and vary across cell types. Throughout Drosophila developmental stages (embryo, larva, pupa and adult), polyploid cells are present in numerous organs and help orchestrate development while contributing to normal growth, well-being and homeostasis of the organism. Conversely, increasing evidence has shown that polyploid cells are prevalent in Drosophila tumors and play important roles in tumor growth and invasiveness. Here, we summarize the genes and pathways involved in polyploidy during normal and tumorigenic development, the mechanisms underlying polyploidization, and the functional aspects of polyploidy in development, homeostasis and tumorigenesis in the Drosophila model.

Keywords: Cancer; Development; Drosophila; Endocycle; Endoreplication; Polyploidy.

Figure 1.

Endomitosis encompasses G1, S, G2 and partial M phase without karyokinesis and cytokinesis. Endocycle comprises the G and S phase. In cell fusion, cells merge, resulting in a multinucleated cell. The mitotic cycle includes G1, S, G2 and M phase and ends with two single nucleated cells.

Figure 2.

Through different Drosophila life cycle stages, polyploid cells promote development and growth in distinct organs.

Figure 3.

Depiction of the endocycle process. Specific expression of cell cycle regulators promotes S and G phase and evasion of M phase.

Figure 4.

Different tumor models in Drosophila containing polyploid-tumor cells. (A) Ectopic expression of oncogenes in combination with tumor suppressor inhibition transforms the wing-disc epithelia into neoplasms containing polyploid giant tumor cells with features that recapitulates certain hallmarks of cancer. (B) Notch hyperactivation promotes neoplastic tumorigenesis in imaginal ring polyploid cells. (C) Polyploid-tumor cells re-enter mitosis and depolyploidization resulting in chromosomal instability.