Browsing by Subject "Polyploid"

Endopolyploid cells (hereafter - polyploid cells), which contain whole genome duplications in an otherwise diploid organism, play vital roles in development and physiology of diverse organs such as our heart and liver. Polyploidy is also observed with high frequency in many tumors, and division of such cells frequently creates aneuploidy (chromosomal imbalances), a hallmark of cancer. Despite its frequent occurrence and association with aneuploidy, little is known about the specific role that polyploidy plays in diverse contexts. Using a new model tissue, the Drosophila rectal papilla, we sought to uncover connections between polyploidy and aneuploidy during organ development. Our lab previously discovered that the papillar cells of the Drosophila hindgut undergo developmentally programmed polyploid cell divisions, and that these polyploid cell divisions are highly error-prone. Time-lapse studies of polyploid mitosis revealed that the papillar cells undergo a high percentage of tripolar anaphase, which causes extreme aneuploidy. Despite this massive chromosome imbalance, we found the tripolar daughter cells are viable and support normal organ development and function, suggesting acquiring extra genome sets enables a cell to tolerate the genomic alterations incurred by aneuploidy. We further extended these findings by seeking mechanisms by which the papillar cells tolerated this resultant aneuploidy.

Polyploid cells are generated through a cell cycle variant termed the endocycle. Endocycling cells undergo multiple rounds of genome duplication without an intervening mitosis. Endocycling is known to lead to alterations in chromosomes structure that make mitosis “ill advised”, in the words of one review. However, many polyploid cells retain mitotic capacity, both when polyploidy is induced pathologically, and in some developmental contexts. Using two mitotic polyploid cell types in Drosophila melanogaster, I investigated how chromosomes structure is regulated in pathological and developmental endocycles. By combining genetics, live imaging and chromosome cytology I have discovered two phases of chromosome regulation that, together, ensure accurate mitosis in polyploid cells. The first of these occurs during the endocycle when removal of sister chromatid cohesin by pds5, without mitosis, allows for the formation of paired chromatids. We named this process “cohesin disestablishment”. Secondly, during cell division, mad2 controls the length of mitosis which allows time for sister chromatids to separate into pairs. We named this process “Separation Into Recent Sisters” (SIRS). Together, cohesin disestablishment and SIRS, allow the accurate segregation of chromosomes in polyploid mitotic cells.