Cyclin A Associates with the Fusome during Germline Cyst Formation in the Drosophila Ovary

Abstract

Regulated changes in the cell cycle underlie many aspects of growth and differentiation. Prior to meiosis, germ cell cycles in many organisms become accelerated, synchronized, and modified to lack cytokinesis. These changes cause cysts of interconnected germ cells to form that typically contain 2(n) cells. In Drosophila, developing germ cells during this period contain a distinctive organelle, the fusome, that is required for normal cyst formation. We find that the cell cycle regulator Cyclin A transiently associates with the fusome during the cystocyte cell cycles, suggesting that fusome-associated Cyclin A drives the interconnected cells within each cyst synchronously into mitosis. In the presence of a normal fusome, overexpression of Cyclin A forces cysts through an extra round of cell division to produce cysts with 32 germline cells. Female sterile mutations in UbcD1, encoding an E2 ubiquitin-conjugating enzyme, have a similar effect. Our observations suggest that programmed changes in the expression and cytoplasmic localization of key cell cycle regulatory proteins control germline cyst production.

Bam and Otu can regulate stem cell fate by stabilizing cyclin A

“…The specific and opposite roles of CycA and CycB in the GSC remain to be elucidated. They cannot substitute for each other in GSCs and may thus have specific targets in GSCs, or may even act more specifically on the ability to receive or transduce self-renewal signals (17,21). The Ji et al (7) work demonstrates that the essential but not conserved differentiation factor Bam regulates the stability of CycA, and therefore the GSC ability to self-renew.…”

Regulation of Cyclin A protein in meiosis and early embryogenesis

“…In Drosophila oogenesis Cyclin A levels must be controlled precisely for oocyte differentiation and for the onset of meiosis. The mitotic divisions early in oogenesis that produce the oocyte and its sister nurse cells are dependent on Cyclin A (14). Although these cells are connected by cytoplasmic bridges, solely the oocyte goes through meiosis, while the nurse cells become polyploid by the endo cycle.…”

Bam-dependent deubiquitinase complex can disrupt germ-line stem cell maintenance by targeting cyclin A

“…While it is observed as a spherical dot in GSCs/CBs, the fusome progressively grows upon cell division to become elongated and finally a branched structure in matured cysts. Because a significant proportion of CycA is associated with the fusome, regulation of CycA at the fusome likely plays important roles in controlling asymmetric division of GSCs and germ cell-specific mitosis (21). Interestingly, previous and current studies have shown that Bam is partially associated with the fusome and required to promote proper incomplete cytokinesis (detailed information shown in SI Text and Fig.…”

“…Second, ectopic expression of either Bam or CycA leads to a GSC-loss phenotype (5,22). Third, cycA has been shown to genetically interact with bam to control germ cell cyst division (21). To explore the biochemical relationship between Bam and CycA, we first determined whether Bam and CycA form a complex by performing immunoprecipitation assays.…”

“…In Drosophila, it has been proposed that GSC fate determination is tightly regulated by a specific cell cycle program (19,20). Previous studies have revealed that mutation or dysregulated expression of cyclin proteins, such as cyclin A (CycA), cyclin B (CycB), and cyclin E (CycE), result in defects of GSC maintenance, differentiation, and/or an abnormal cell number of (32-or 8-cell) cysts (19)(20)(21)(22)(23). Thus, proper expression of cyclin proteins is critical for GSC fate determination and/or normal germ-line development.…”