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<jats:sec> <jats:title>INTRODUCTION</jats:title> <jats:p>Centrioles are small microtubule-based cellular structures that are critical for cilia and centrosome assembly. During successful fertilization in animals, centrioles are asymmetrically inherited. Centrioles are eliminated from the egg and contributed by the sperm. Paternal centrioles organize the first zygote centrosome, the major microtubule-organizing center that ensures proper mitotic progression and successful embryo development. Centriole elimination from the oocyte during development is thought to ensure correct centriole number and proper mitosis upon fertilization, and to prevent parthenogenesis (i.e., embryonic development without fertilization).</jats:p> </jats:sec> <jats:sec> <jats:title>RATIONALE</jats:title> <jats:p> Centrioles are thought to be exceptionally stable structures, so their disappearance in oogenesis is paradoxical and the elimination mechanism remains elusive. In addition, the consequences of retaining maternal centrioles for oogenesis progression, meiosis, and reproduction are unclear. Here, we used <jats:italic>Drosophila melanogaster</jats:italic> oogenesis to identify the molecular mechanisms underlying centriole elimination and the consequences of preventing it. </jats:p> </jats:sec> <jats:sec> <jats:title>RESULTS</jats:title> <jats:p> To investigate the mechanism of centriole elimination, we first looked into the timing and order of disappearance of multiple centrosome components. Each centrosome is composed of two centrioles and a surrounding pericentriolar matrix (PCM) that is important for microtubule nucleation. <jats:italic>Drosophila</jats:italic> oocytes inherit all centrosomes from their neighboring nurse cells, which form a large microtubule-organizing center. We analyzed multiple markers along oogenesis process and found that centrosome elimination occurs in astepwise manner: First, centrosomes lost PCM components, whereas centriole components only disappeared in the last stages of oogenesis before meiotic division. Because Polo kinase is the major PCM recruitment factor, we then investigated the regulation of this protein in theoocyte microtubule-organizing center. Polo was down-regulated in similar stages, as were the PCM components. We thus hypothesized that Polo is important for PCM maintenance and that the PCM protects centrioles from elimination. To confirm this prediction, we depleted either Polo or the PCM, or both together, in <jats:italic>Drosophila</jats:italic> cultured cells arrested in S phase (where centriole content is maintained constant). In all cases, we observed centriole loss. Moreover, depletion of Polo in oogenesis induced premature centriole elimination. </jats:p> <jats:p>To test the hypothesis that Polo and the PCM are critical for centriole maintenance, we ectopically expressed a Polo kinase that localizes to the oocyte’s centrioles. Expression of this protein prevented PCM loss and maintained functional centrioles even during meiotic division, when normally they would all have been eliminated, supporting our hypothesis. Finally, we investigated the consequences of maintaining centrioles in the female germ line. Retained centrioles nucleated microtubules that interfered with meiotic divisions. Despite this, centriole-containing oocytes were fertilized but could only undergo very few divisions, arresting very early in development.</jats:p> </jats:sec> <jats:sec> <jats:title>CONCLUSIONS</jats:title> <jats:p>Our study revealed that centriole stability is not an intrinsic property of those structures, as previously thought, but requires a Polo kinase– and PCM-dependent maintenance program. By artificially maintaining this program, we retained maternal centrosomes through oogenesis, which led to defective meiosis and aborted early embryonic development. We propose that regulation of this centriole maintenance program is essential for successful sexual reproduction and is likely to define centriole life span in different tissues, thereby shaping the cytoskeleton.</jats:p> <jats:fig fig-type="figure" orientation="portrait" position="float"> <jats:caption> <jats:title>Down-regulation of a Polo- and PCM-dependent centriole maintenance program leads to centriole elimination in oogenesis and successful embryonic development.</jats:title> <jats:p>In early oogenesis stages, centrioles from nurse cells migrate to the oocyte, forming a large microtubule organizing center. Polo and the pericentriolar matrix (PCM) that surrounds centrioles are lost from the centrioles in middle and late stages, leading to centriole elimination before meiotic division. By anchoring Polo (and consequently PCM) to the oocyte centrioles, centrioles are maintained throughout oogenesis, leading to abnormal meiotic and mitotic divisions and consequently failed zygotic development.</jats:p> </jats:caption> <jats:graphic xmlns:xlink="http://www.w3.org/1999/xlink" orientation="portrait" position="float" xlink:href="353_aaf4866_Fa.jpeg" /> </jats:fig> </jats:sec>

<jats:p>Last week's dramatic vote by the United Kingdom (UK) to leave the European Union (EU) was the culmination of a heated referendum campaign that questioned the value of partnerships between the UK and the EU. Now, with many bridges burned—or at least charred—where do political leaders go next? Politicians in the UK and EU are going to need every available foundation on which to rebuild trust and mutual interests. They will need to discover once again how to work in partnership. It will be a long and difficult process; one in which science should play a crucial role.</jats:p>

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