Mechanisms of germ cell development in Drosophila oogenesis.

Abstract

Germ cell development requires interplay between factors that control cell fate and division. Early in their development, germ cells are an interconnected group of mitotically dividing cells. Key regulatory events then lead to the specification of mature gametes, and is also marked by the switch to a meiotic cell cycle program. Though the events required for gamete specification and the regulation of meiosis are well understood, how each of these events are coordinated during development remain unclear. The adult Drosophila ovary continuously produces germ cells throughout the organism's lifetime, but many of the cellular processes that occur during mammalian gamete development are conserved. Drosophila ovaries produce oocytes through the actions of asymmetrically germline stem cells (GSCs), which give rise to a differentiated daughter cell (the cystoblast), while self-renewing to replenish the stem cell pool. The cystoblast divides four times with incomplete cytokinesis; fifteen daughter cells give rise to endocycling nurse cells, while the remaining cell is specified as the oocyte. To further understand the mechanisms that lead to proper cyst divisions, we analyzed the germ cell cycles using the Fluorescence Ubiquitin Cell Cycle Indicator (FUCCI) system. We found that cell cycle regulator activity changes dramatically upon germ cell development, presumably to prepare for the specialized cell cycles that occur upon oocyte specification. Identification of the nucleocytoplasmic transport receptor Transportin-Serine/Arginine rich as a key regulator of germ cell divisions and cell fate specification allowed us to further probe the role of cell cycle timing in the proper acquisition of fate. Together, these findings provide insight into the balance between germ cell division and fate, and identify key developmental checkpoints for proper oocyte specification.