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      A celebration of the 25th anniversary of chromatin-mediated spindle assembly

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      a , a , b , * ,
      Molecular Biology of the Cell
      The American Society for Cell Biology

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          Abstract

          Formation of a bipolar spindle is required for the faithful segregation of chromosomes during cell division. Twenty-five years ago, a transformative insight into how bipolarity is achieved was provided by Rebecca Heald, Eric Karsenti, and colleagues in their landmark publication characterizing a chromatin-mediated spindle assembly pathway in which centrosomes and kinetochores were dispensable. The discovery revealed that bipolar spindle assembly is a self-organizing process where microtubules, which possess an intrinsic polarity, polymerize around chromatin and become sorted by mitotic motors into a bipolar structure. On the 25 th anniversary of this seminal paper, we discuss what was known before, what we have learned since, and what may lie ahead in understanding the bipolar spindle.

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          Most cited references86

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          Dynamic instability of microtubule growth.

          We report here that microtubules in vitro coexist in growing and shrinking populations which interconvert rather infrequently. This dynamic instability is a general property of microtubules and may be fundamental in explaining cellular microtubule organization.
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            Self-organization of microtubules into bipolar spindles around artificial chromosomes in Xenopus egg extracts.

            Functional nuclei and mitotic spindles are shown to assemble around DNA-coated beads incubated in Xenopus egg extracts. Bipolar spindles assemble in the absence of centrosomes and kinetochores, indicating that bipolarity is an intrinsic property of microtubules assembling around chromatin in a mitotic cytoplasm. Microtubules nucleated at dispersed sites with random polarity rearrange into two arrays of uniform polarity. Spindle-pole formation requires cytoplasmic dynein-dependent translocation of microtubules across one another. It is proposed that spindles form in the absence of centrosomes by motor-dependent sorting of microtubules according to their polarity.
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              Flies without centrioles.

              Centrioles and centrosomes have an important role in animal cell organization, but it is uncertain to what extent they are essential for animal development. The Drosophila protein DSas-4 is related to the human microcephaly protein CenpJ and the C. elegans centriolar protein Sas-4. We show that DSas-4 is essential for centriole replication in flies. DSas-4 mutants start to lose centrioles during embryonic development, and, by third-instar larval stages, no centrioles or centrosomes are detectable. Mitotic spindle assembly is slow in mutant cells, and approximately 30% of the asymmetric divisions of larval neuroblasts are abnormal. Nevertheless, mutant flies develop with near normal timing into morphologically normal adults. These flies, however, have no cilia or flagella and die shortly after birth because their sensory neurons lack cilia. Thus, centrioles are essential for the formation of centrosomes, cilia, and flagella, but, remarkably, they are not essential for most aspects of Drosophila development.
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                Author and article information

                Contributors
                Role: Monitoring Editor
                Journal
                Mol Biol Cell
                Mol Biol Cell
                molbiolcell
                mboc
                Molecular Biology of the Cell
                The American Society for Cell Biology
                1059-1524
                1939-4586
                01 February 2022
                25 January 2022
                : 33
                : 2
                : rt1
                Affiliations
                [a ]Biology Department, University of Massachusetts, Amherst, Amherst, MA 01003
                [b ]Molecular and Cellular Biology Graduate Program, University of Massachusetts, Amherst, Amherst, MA 01003
                University of Virginia
                Author notes
                *Address correspondence to: Thomas J. Maresca ( tmaresca@ 123456umass.edu ).
                Article
                E21-08-0400
                10.1091/mbc.E21-08-0400
                9236140
                35076260
                029f3448-bf0c-4728-a495-f31cd5e9a8f7
                © 2022 Verma and Maresca. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.

                This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial-Share Alike 4.0 International Creative Commons License.

                History
                : 01 October 2021
                : 18 November 2021
                : 19 November 2021
                Categories
                Retrospective

                Molecular biology
                Molecular biology

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