Male meiotic spindle features that efficiently segregate paired and lagging chromosomes

  1. Gunar Fabig  Is a corresponding author
  2. Robert Kiewisz
  3. Norbert Lindow
  4. James A Powers
  5. Vanessa Cota
  6. Luis J Quintanilla
  7. Jan Brugués
  8. Steffen Prohaska
  9. Diana S Chu
  10. Thomas Müller-Reichert  Is a corresponding author
  1. Technische Universität Dresden, Germany
  2. Zuse Institute Berlin, Germany
  3. Indiana University, United States
  4. San Francisco State University, United States
  5. Max Planck Institute, Germany

Abstract

Chromosome segregation during male meiosis is tailored to rapidly generate multitudes of sperm. Little is known about mechanisms that efficiently partition chromosomes to produce sperm. Using live imaging and tomographic reconstructions of spermatocyte meiotic spindles in Caenorhabditis elegans, we find the lagging X chromosome, a distinctive feature of anaphase I in C. elegans males, is due to lack of chromosome pairing. The unpaired chromosome remains tethered to centrosomes by lengthening kinetochore microtubules, which are under tension, suggesting that a 'tug of war' reliably resolves lagging. We find spermatocytes exhibit simultaneous pole-to-chromosome shortening (anaphase A) and pole-to-pole elongation (anaphase B). Electron tomography unexpectedly revealed spermatocyte anaphase A does not stem solely from kinetochore microtubule shortening. Instead, movement of autosomes is largely driven by distance change between chromosomes, microtubules, and centrosomes upon tension release during anaphase. Overall, we define novel features that segregate both lagging and paired chromosomes for optimal sperm production.

Data availability

Data have been uploaded to the TU Dresden Open Access Repository and Archive system (OpARA) and are available as open access: http://dx.doi.org/10.25532/OPARA-56

The following data sets were generated

Article and author information

Author details

  1. Gunar Fabig

    Experimental Center, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
    For correspondence
    gunar.fabig@tu-dresden.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3017-0978
  2. Robert Kiewisz

    Experimental Center, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2733-4978
  3. Norbert Lindow

    Visualization and Data Analysis, Zuse Institute Berlin, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. James A Powers

    Light Microscopy Imaging Center, Indiana University, Bloomington, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Vanessa Cota

    Department of Biology, San Francisco State University, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Luis J Quintanilla

    Department of Biology, San Francisco State University, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Jan Brugués

    Molecular Cell Biology and Genetics, Max Planck Institute, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  8. Steffen Prohaska

    Visualization and Data Analysis, Zuse Institute Berlin, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  9. Diana S Chu

    Department of Biology, San Francisco State University, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Thomas Müller-Reichert

    Experimental Center, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
    For correspondence
    mueller-reichert@tu-dresden.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0203-1436

Funding

Deutsche Forschungsgemeinschaft (MU 1423/10-1)

  • Gunar Fabig
  • Thomas Müller-Reichert

Horizon 2020 Framework Programme (No. 675737)

  • Robert Kiewisz
  • Thomas Müller-Reichert

National Institutes of Health (R03 HD093990-01A1)

  • Vanessa Cota
  • Diana S Chu

National Science Foundation (RUI-1817611,DBI-1548297)

  • Vanessa Cota
  • Diana S Chu

National Institutes of Health (NIH1S10OD024988-01)

  • James A Powers

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Yukiko M Yamashita, University of Michigan, United States

Publication history

  1. Received: August 9, 2019
  2. Accepted: March 8, 2020
  3. Accepted Manuscript published: March 9, 2020 (version 1)
  4. Accepted Manuscript updated: March 10, 2020 (version 2)
  5. Version of Record published: March 27, 2020 (version 3)
  6. Version of Record updated: April 1, 2020 (version 4)

Copyright

© 2020, Fabig et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 2,276
    Page views
  • 344
    Downloads
  • 7
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Gunar Fabig
  2. Robert Kiewisz
  3. Norbert Lindow
  4. James A Powers
  5. Vanessa Cota
  6. Luis J Quintanilla
  7. Jan Brugués
  8. Steffen Prohaska
  9. Diana S Chu
  10. Thomas Müller-Reichert
(2020)
Male meiotic spindle features that efficiently segregate paired and lagging chromosomes
eLife 9:e50988.
https://doi.org/10.7554/eLife.50988

Further reading

    1. Cell Biology
    2. Cancer Biology
    Chelsea U Kidwell, Joseph R Casalini ... Minna Roh-Johnson
    Research Article Updated

    Recent studies reveal that lateral mitochondrial transfer, the movement of mitochondria from one cell to another, can affect cellular and tissue homeostasis. Most of what we know about mitochondrial transfer stems from bulk cell studies and have led to the paradigm that functional transferred mitochondria restore bioenergetics and revitalize cellular functions to recipient cells with damaged or non-functional mitochondrial networks. However, we show that mitochondrial transfer also occurs between cells with functioning endogenous mitochondrial networks, but the mechanisms underlying how transferred mitochondria can promote such sustained behavioral reprogramming remain unclear. We report that unexpectedly, transferred macrophage mitochondria are dysfunctional and accumulate reactive oxygen species in recipient cancer cells. We further discovered that reactive oxygen species accumulation activates ERK signaling, promoting cancer cell proliferation. Pro-tumorigenic macrophages exhibit fragmented mitochondrial networks, leading to higher rates of mitochondrial transfer to cancer cells. Finally, we observe that macrophage mitochondrial transfer promotes tumor cell proliferation in vivo. Collectively these results indicate that transferred macrophage mitochondria activate downstream signaling pathways in a ROS-dependent manner in cancer cells, and provide a model of how sustained behavioral reprogramming can be mediated by a relatively small amount of transferred mitochondria in vitro and in vivo.

    1. Cell Biology
    2. Developmental Biology
    Yalda Afshar, Feyiang Ma ... Luisa Iruela-Arispe
    Research Article

    Environmental cues, such as physical forces and heterotypic cell interactions play a critical role in cell function, yet their collective contributions to transcriptional changes are unclear. Focusing on human endothelial cells, we performed broad individual sample analysis to identify transcriptional drifts associated with environmental changes that were independent of genetic background. Global gene expression profiling by RNAseq and protein expression by LC-MS directed proteomics distinguished endothelial cells in vivo from genetically matched culture (in vitro) samples. Over 43% of the transcriptome was significantly changed by the in vitro environment. Subjecting cultured cells to long-term shear stress significantly rescued the expression of approximately 17% of genes. Inclusion of heterotypic interactions by co-culture of endothelial cells with smooth muscle cells normalized approximately 9% of the original in vivo signature. We also identified novel flow dependent genes, as well as genes that necessitate heterotypic cell interactions to mimic the in vivo transcriptome. Our findings highlight specific genes and pathways that rely on contextual information for adequate expression from those that are agnostic of such environmental cues.