title: Indispensable pre-mitotic endocycles promote aneuploidy in the Drosophila rectum.
abstract: The endocycle is a modified cell cycle that lacks M phase. Endocycles are well known for enabling continued growth of post-mitotic tissues. By contrast, we discovered pre-mitotic endocycles in precursors of Drosophila rectal papillae (papillar cells). Unlike all known proliferative Drosophila adult precursors, papillar cells endocycle before dividing. Furthermore, unlike diploid mitotic divisions, these polyploid papillar divisions are frequently error prone, suggesting papillar structures may accumulate long-term aneuploidy. Here, we demonstrate an indispensable requirement for pre-mitotic endocycles during papillar development and also demonstrate that such cycles seed papillar aneuploidy. We find blocking pre-mitotic endocycles disrupts papillar morphogenesis and causes organismal lethality under high-salt dietary stress. We further show that pre-mitotic endocycles differ from post-mitotic endocycles, as we find only the M-phase-capable polyploid cells of the papillae and female germline can retain centrioles. In papillae, this centriole retention contributes to aneuploidy, as centrioles amplify during papillar endocycles, causing multipolar anaphase. Such aneuploidy is well tolerated in papillae, as it does not significantly impair cell viability, organ formation or organ function. Together, our results demonstrate that pre-mitotic endocycles can enable specific organ construction and are a mechanism that promotes highly tolerated aneuploidy.
authors.affiliation: Department of Pharmacology and Cancer Biology, Box 3813, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Schoenfelder
authors.affiliation: Department of Pharmacology and Cancer Biology, Box 3813, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Montague
authors.affiliation: Department of Pharmacology and Cancer Biology, Box 3813, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Sarah V
authors.initials: SV
authors.lastname: Paramore
authors.affiliation: Department of Pharmacology and Cancer Biology, Box 3813, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Ashley L
authors.initials: AL
authors.lastname: Lennox
authors.affiliation: Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Mahowald
authors.affiliation: Department of Pharmacology and Cancer Biology, Box 3813, Duke University Medical Center, Durham, NC 27710, USA don.fox@duke.edu.
authors.forename: Donald T
authors.initials: DT
authors.lastname: Fox
mesh_terms: D000782:Aneuploidy; D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D002502:Centrioles / Q000502:physiology; D004330:Drosophila / Q000235:genetics* / Q000254:growth & development; D007091:Image Processing, Computer-Assisted; D020287:In Situ Nick-End Labeling; D007814:Larva / Q000254:growth & development; D018613:Microscopy, Confocal; D038081:Organogenesis / Q000502:physiology*; D012007:Rectum / Q000166:cytology* / Q000254:growth & development
keywords: Aneuploidy; Centrosome; Drosophila; Endocycle; Multipolar; Polyploidy