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.

Proliferation of Double-Strand Break-Resistant Polyploid Cells Requires Drosophila FANCD2

“…During 2 nd larval instar, papillar precursors endocycle, producing octoploid nuclei (Fox et al 2010; Schoenfelder et al 2014). Unlike previously studied examples of endocycled cells with an inactive DDR, papillar cells then undergo polyploid divisions.…”

Polyteny: still a giant player in chromosome research

“…This compromise allows endocycling cells to focus cellular resources elsewhere. In support of this model, many polyploid Drosophila cell types down-regulate factors required for replication and components of the mitotic cell cycle, such as centrosomes (Schoenfelder et al 2014; Nordman et al 2011; Maqbool et al 2010; Mahowald et al 1979; Mahowald and Strassheim 1970). …”

When bigger is better: the role of polyploidy in organogenesis

“…The mitotic divisions of the 8C cells are marked by high chromosome segregation errors. Despite this, analysis of loss of function for the Fizzy-related protein, an activator of the Anaphase Promoting Complex necessary for endocycles, indicates that endocycles are necessary in rectal papillar cells for proper organogenesis of the rectum [36]. …”