Aurora B and C kinases regulate chromosome desynapsis and segregation during mouse and human spermatogenesis

Abstract

Precise control of chromosome dynamics during meiosis is critical for fertility. A gametocyte undergoing meiosis coordinates formation of the synaptonemal complex (SC) to promote efficient homologous chromosome recombination. Subsequent disassembly of the SC occurs prior to segregation of homologous chromosomes during meiosis I. We examined the requirements of the mammalian Aurora kinases (AURKA, AURKB and AURKC) during SC disassembly and chromosome segregation using a combination of chemical inhibition and gene deletion approaches. We find that both mouse and human spermatocytes fail to disassemble SC lateral elements when the kinase activity of AURKB and AURKC are chemically inhibited. Interestingly, both Aurkb conditional knockout and Aurkc knockout mouse spermatocytes successfully progress through meiosis, and the mice are fertile. In contrast, Aurkb, Aurkc double knockout spermatocytes fail to coordinate disassembly of SC lateral elements with chromosome condensation and segregation, resulting in delayed meiotic progression. In addition, deletion of Aurkb and Aurkc leads to an accumulation of metaphase spermatocytes, chromosome missegregation and aberrant cytokinesis. Collectively, our data demonstrate that AURKB and AURKC functionally compensate for one another ensuring successful mammalian spermatogenesis.