Analysis of a hypomorphic mei-P26 mutation reveals developmental control of CO patterning mechanisms

Female gametogenesis in Drosophila requires both differentiation of germline stem cells and the unique cell cycle meiosis. Successful segregation of chromosomes into gametes during meiosis requires the formation of crossovers between homologous chromosomes. The frequency and distribution of crossovers is highly regulated at several levels, including formation of at least one obligate crossover per pair of homologs, crossover interference that keeps crossovers farther apart than expected by chance, and suppression of crossovers in and near the centromere. To achieve crossover patterning, a meiosis specific version of homologous recombination is used to repair programmed double-stranded breaks, and in Drosophila melanogaster, this recombination pathway requires the putative double Holliday junction resolvase MEI-9. Despite our understanding of crossover patterning mechanisms at the phenomenological level, how crossover patterning mechanisms are developmentally controlled in the context of germ cell differentiation is unknown. Here, we take advantage of a hypomorphic mutation in mei-P26, a gene previously associated with regulation of both germ cell mitoses and meiotic induction. We confirm that mei-P261 mutants show extended expression of mitotic cell cycle markers but rarely completely block differentiation, indicating that the mitotic cell cycle is mis-regulated. In this developmentally delayed context, we show that mei-P261 mutants enter meiosis and complete the earliest stages of prophase, including loading of synaptonemal complex proteins onto the centromere and initial loading onto the arms. Most nuclei do not progress past this to make full length synaptonemal complex, yet meiotic double-strand breaks are induced and crossovers form. However, while these crossovers require MEI-9 and exhibit crossover assurance, the centromere effect and interference are lost. We suggest a model where entry into zygotene of prophase is enough to commit pro-oocytes to using the meiotic homologous recombination machinery and thus ensuring crossover assurance, but that full length synaptonemal complex assembly is required for crossover interference.