The small GTPase Ran and β-importins Tnpo-SR and Cadmus promote ovarian cyst formation in Drosophila

Abstract

Germ cells follow a precise and coordinated molecular timeline to produce a viable oocyte. While undergoing mitotic expansion via incomplete cytokinesis, cysts of undifferentiated cells form and remain interconnected prior to meiotic initiation, through mechanisms that are not well-defined. In somatic cells, Ras-related nuclear protein (Ran) spatiotemporally regulates mitotic spindle assembly, cleavage furrow formation and abscission. Here, we identify Ran and [beta]-importins as critical regulators of cyst development in the Drosophila ovary. Depletion of Ran or the [beta]-importins Tnpo-SR and Cadmus results in egg chambers with variable numbers of germ cells, suggesting abnormal cyst development and cyst fragmentation, and consequently disrupts oocyte selection. We demonstrate that Ran, Tnpo-SR, and Cadmus regulate key cellular processes during cyst formation, including cell cycle dynamics, fusome biogenesis, and ring canal stability, all independently of mitotic spindle assembly. Further, Tnpo-SR and Cadmus control cyclin accumulation and suppress cytokinesis, suggesting that [beta]-importins sequester protein cargos that normally promote the mitotic-to-meiotic transition. Our data demonstrates that Ran and [beta]-importins are critical for the cell fate decisions of germ cells, a role that is likely conserved in other organisms.