Abstract

It is well known that cyclin B3 (cycB3) plays a key role in the control of cell cycle progression. However, whether cycB3 is involved in stem cell fate determination remains unknown. The Drosophila ovary provides an exclusive model for studying the intrinsic and extrinsic factors that modulate the fate of germline stem cells (GSCs). Here, using this model, we show that Drosophila cycB3 plays a new role in controlling the fate of germline stem cells (GSC). Results from cycB3 genetic analyses demonstrate that cycB3 is intrinsically required for GSC maintenance. Results from green fluorescent protein (GFP)-transgene reporter assays show that cycB3 is not involved in Dad-mediated regulation of Bmp signaling, or required for dpp-induced bam transcriptional silencing. Double mutants of bam and cycB3 phenocopied bam single mutants, suggesting that cycB3 functions in a bam-dependent manner in GSCs. Deficiency of cycB3 fails to cause apoptosis in GSCs or influence cystoblast (CB) differentiation into oocytes. Furthermore, overexpression of cycB3 dramatically increases the CB number in Drosophila ovaries, suggesting that an excess of cycB3 function delays CB differentiation. Given that the cycB3 gene is evolutionarily conserved, from insects to humans, cycB3 may also be involved in controlling the fate of GSCs in humans.

Highlights

  • Adult stem cells are characterized by their ability to supply new cells to replace aged/injured cells in adult tissues throughout life, and to maintain their “stemness”, via self-renewal

  • Germline stem cells (GSCs) in the Drosophila ovary provide an excellent model for exploring the mechanisms underlying GSC fate determination, in vivo

  • To discover the genes that possibly influence the fate of Drosophila GSCs, we performed a genetic screen of female sterile lines

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Summary

Introduction

Adult stem cells are characterized by their ability to supply new cells to replace aged/injured cells in adult tissues throughout life, and to maintain their “stemness”, via self-renewal. It is essential for stem cells to keep a balance between self-renewal and differentiation into daughter cells. Germline stem cells (GSCs) in the Drosophila ovary provide an excellent model for exploring the mechanisms underlying GSC fate determination, in vivo. Two to three GSCs are located in the anterior region of the germarium, and three types of somatic cells (terminal filament cells, cap cells and escort stem cells) constitute the microenvironment ( called the “niche”) for GSCs (Figure 1A) [3,4]. A GSC divides asymmetrically to give birth to two daughters—one daughter cell remains adherent to niche cells and continuously functions as a stem cell, whereas the other daughter moves away from the niche and initiates differentiation as a cystoblast (CB). GSCs are readily visualized by a spherical spectrosome, which is located in the anterior region in the cell, while the spectrosome in CB usually loses its anterior

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