Aurora B and C kinases regulate prophase exit and chromosome segregation during 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 is required prior to meiotic divisions to ensure accurate segregation of chromosomes. We examined the requirements of the mammalian Aurora kinases (AURKA, B, and C) 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 AURKB and AURKC are inhibited. Interestingly, both Aurkb conditional knockout and Aurkc knockout spermatocytes successfully progress through meiosis and mice are fertile. In contrast, Aurkb, Aurkc double knockout spermatocytes failed to coordinate disassembly of SC lateral elements with chromosome segregation, resulting in delayed meiotic progression, spindle assembly checkpoint failure, chromosome missegregation, and abnormal spermatids. Collectively, our data demonstrates that AURKB and AURKC functionally compensate for one another ensuring successful mammalian spermatogenesis.SUMMARYChemical inhibition and gene deletion approaches show that Aurora B and Aurora C have overlapping functions that ensure timely disassembly of lateral element components of the synaptonemal complex in mouse and human spermatocytes and ensure accurate chromosome segregation during meiosis.

Testicular Localization and Potential Function of Vimentin Positive Cells during Spermatogonial Differentiation Stages

“…AURKB and AURKC ensure the organization of chromosome restructuring events during the MI/G2 transition during the spermatogenic process, and they are vital for accurate chromosome segregation. [8,9] Pik3r1 Phosphatidylinositol 3-kinase regulatory subunit alpha; binds to activated (phosphorylated) protein-Tyr kinases through its SH2 domain and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane.…”

“…Some recent studies showed that AURKB and AURKC ensure the organization of chromosomal restructuring during the MI/G2 transition during the spermatogenesis process, and they maintain ordered system meiosis that is critical for accurate chromosome segregation [6]. Snai1 mediates developmental changes during cellular transitions in spermatogenesis [9]. Another protein cofunction with vimentin is Mmp2, which specifically regulates the survival or apoptosis of spermatocytes [5].…”

“…The cytoskeleton, which accommodates actin, microtubules, and intermediate filaments, characterizes those cells' activities [5,7]. One of the critical cytoskeletons that play crucial functions in these spermatogenic processes is vimentin [8,9].…”