Overlapping roles for PLK1 and Aurora A during meiotic centrosome biogenesis in mouse spermatocytes

Abstract

The establishment of bipolar spindles during meiotic divisions ensures faithful chromosome segregation to prevent gamete aneuploidy. We analyzed centriole duplication, as well as centrosome maturation and separation during meiosis I and II using mouse spermatocytes. The first round of centriole duplication occurs during early prophase I, and then, centrosomes mature and begin to separate by the end of prophase I to prime formation of bipolar metaphase I spindles. The second round of centriole duplication occurs at late anaphase I, and subsequently, centrosome separation coordinates bipolar segregation of sister chromatids during meiosis II. Using a germ cell‐specific conditional knockout strategy, we show that Polo‐like kinase 1 and Aurora A kinase are required for centrosome maturation and separation prior to metaphase I, leading to the formation of bipolar metaphase I spindles. Furthermore, we show that PLK1 is required to block the second round of centriole duplication and maturation until anaphase I. Our findings emphasize the importance of maintaining strict spatiotemporal control of cell cycle kinases during meiosis to ensure proficient centrosome biogenesis and, thus, accurate chromosome segregation during spermatogenesis.

Aurora kinase A is essential for meiosis in mouse oocytes

“…Mice possessing loxP sites flanking exon 3 of the Aurka gene [ 33 ] were obtained from (C57BL/6N; Aurkatm1c(EUCOMM)Hmgu/J) the International Mouse Phenotyping Consortium (IMPC; www.mousephenotype.org ). To generate Aurka fl/fl Gdf9-Cre mice, female mice carrying the Aurka floxed alleles were crossed with Gdf9-Cre males (Jackson Laboratories Tg (Gdf9-icre)5092Coo/J, #011062).…”

“…To test if AURKC can compensate for loss of AURKA, and to further understand the role of AURKA during meiosis in mouse oocytes, we generated a mouse strain that lacks Aurka [ 33 ] specifically in oocytes using Gdf9 -mediated Cre excision [ 34 ]. Consistent with AURKA being the most abundant AURK in oocytes [ 31 ], we demonstrate that AURKA is essential for oocyte maturation through fragmenting aMTOCs, regulating localization of TACC3 at the spindle and may have an unknown function to promote anaphase onset.…”

Haspin participates in Aurora phosphorylation at centromeres and contributes to chromosome congression in male mouse meiosis

“…AURKA, AURKB and AURKC belong to a family of kinases with high sequence homology (Tang et al, 2017). AURKA participates in centrosomes dynamics in male mouse meiosis (Alfaro et al, 2021;Wellard et al, 2021), while AURKB and AURKC (hereafter denoted collectively as AURKB/C) function as the catalytic subunit of the CPC, presenting overlapping functions in spermatogenesis (Jordan et al 2021).…”

“…The gain or loss of chromosomes often originates from dysregulation of centromere assembly, errors in kinetochore-microtubule interaction, or chromosome congression failures. These processes are highly regulated and well-orchestrated by several master regulators, such as PLK1 and Aurora B kinase (AURKB) among others, which perform their role in both mitosis (Lukasiewicz and Lingle, 2009;Nikonova et al, 2013;Schmucker and Sumara, 2014) and meiosis (Alfaro et al, 2021;Wellard et al, 2021). A recently described and poorly studied regulator is the kinase Haspin.…”

Evolution, Expression and Meiotic Behavior of Genes Involved in Chromosome Segregation of Monotremes

“…Thus, AURKs are clearly involved in the regulation of chromosome segregation. However, very little is known about expression or functions of AURKs when it comes to meiosis—some studies have confirmed that, for instance, AURKA together with Polo-like kinase 1 (PLK1) is required for the correct migration of duplicated centrosomes at male meiosis I and II in order to form a bipolar spindle [ 8 , 9 ]. Furthermore, it is unknown why there is the additional isoform AURKC present in germ cells of eutherian mammals, or why it is not present in marsupials.…”