Polyploid Hindgut Cells in Drosophila Undergo Multipolar Mitosis and Tolerate Aneuploidy. Kevin Schoenfelder¹, Ruth Montague², Sarah Paramore², Donald Fox^1,2. 1) Duke University Program in Genetics and Genomics, Durham, NC 27710; 2) Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710.

   Polyploid cells, which contain duplications of their genome, account for most of the biomass of the planet, yet the role and consequences of polyploidy are poorly understood. Polyploidy may be generated by many mechanisms, including entry into an alternate version of the cell cycle that skips M phase, known as the endocycle. Our labs preliminary data demonstrate that the endocycle can result in the amplification of centrosomes, which organize the accurate segregation of chromosomes during mitosis. In 1902, Theodor Boveri proposed that extra centrosomes cause multipolar cell division, subsequent chromosomal imbalance (aneuploidy), and cancer. Since his hypothesis, the viability of such multipolar divisions has been controversial. In either diploid mammalian tumor cell lines or in the Drosophila brain, multipolar metaphases generally resolve into bipolar anaphases, calling into doubt the multipolar cancer generation hypothesis. Centrosome amplification has also been implicated in producing aneuploidy in polyploid cells. However, it remains unclear whether polyploid cells exhibit multipolar division, and whether such divisions yield viable daughter cells. Our lab has addressed this issue in the Drosophila hindgut, a developmental model of polyploid cell division. We find such polyploid cells naturally amplify centrosomes and undergo a surprisingly high rate of multipolar division. Further, genetically increasing the number of cells with extra centrosomes in the developing polyploid hindgut raises the frequency of multipolar polyploid mitosis, yet adult hindgut tissue from these adults remains morphologically and functionally intact, with no detectable cell inviability. These results suggest that 1) the endocycle inhibits mechanisms that normally block multipolar division, and 2) in contrast to diploid cells, polyploid cells tolerate aneuploidy induced by multipolar cell division.