Analysis of a hypomorphic mei-P26 mutation reveals coordination between developmental programming of germ cells and...

Female gametogenesis in Drosophila melanogaster requires differentiation and mitotic division of germ cells, acquisition of oocyte fate, and entry into meiosis. Each of these processes is well understood individually; however, little is known about the mechanisms that ensure proper temporal integration of germ cell differentiation and meiotic chromosome dynamics. Here, we take advantage of a hypomorphic mutation in mei-P26, a well-characterized gene with multiple diverse functions in germ cell development, to determine the consequences of disrupting the coordination between development and meiosis. While null mutations in mei-P26 lead to tumorous ovaries, the hypomorphic allele mei-P261 allows sufficient germ cell differentiation and fertility to support analysis of meiotic chromosome dynamics. Unlike wild-type germaria, 60% of cysts in mei-P261 germaria co-express the differentiation factor Bag of marbles (Bam) and the oocyte specification factor Orb, suggesting that mitotic division is delayed. In this context, the synaptonemal complex rarely assembles into full-length continuous tracks and instead is missing or present only as foci. Despite these phenotypes, meiotic double-strand breaks still form and are repaired as crossovers, but the crossovers are mispatterned and form in centromere proximal regions rather than chromosome arms. The strength of crossover interference is significantly reduced, and the centromere effect is lost, but crossover assurance is intact, and the meiosis-specific machinery is used to form crossovers. We suggest a model where the failure to exit mitosis in a timely fashion causes cells to enter meiosis while still receiving mitotic signals, resulting in abnormal meiotic chromosome dynamics and impaired crossover formation.