Male meiotic spindle features that efficiently segregate paired and lagging chromosomes
- Technische Universität Dresden, Germany
- Zuse Institute Berlin, Germany
- Indiana University, United States
- San Francisco State University, United States
- 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
-
Supplemental data for the publicationOpARA, doi:10.25532/OPARA-56.
Article and author information
Author details
Thomas Müller-Reichert
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
- Yukiko M Yamashita, University of Michigan, United States
Version history
- Received: August 9, 2019
- Accepted: March 8, 2020
- Accepted Manuscript published: March 9, 2020 (version 1)
- Accepted Manuscript updated: March 10, 2020 (version 2)
- Version of Record published: March 27, 2020 (version 3)
- 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
-
- 2,834
- views
-
- 377
- downloads
-
- 16
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
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)
Male meiotic spindle features that efficiently segregate paired and lagging chromosomes
eLife 9:e50988.
https://doi.org/10.7554/eLife.50988
Further reading
-
- Cancer Biology
- Cell Biology
Immune checkpoint inhibitors have produced encouraging results in cancer patients. However, the majority of ß-catenin-mutated tumors have been described as lacking immune infiltrates and resistant to immunotherapy. The mechanisms by which oncogenic ß-catenin affects immune surveillance remain unclear. Herein, we highlighted the involvement of ß-catenin in the regulation of the exosomal pathway and, by extension, in immune/cancer cell communication in hepatocellular carcinoma (HCC). We showed that mutated ß-catenin represses expression of SDC4 and RAB27A, two main actors in exosome biogenesis, in both liver cancer cell lines and HCC patient samples. Using nanoparticle tracking analysis and live-cell imaging, we further demonstrated that activated ß-catenin represses exosome release. Then, we demonstrated in 3D spheroid models that activation of β-catenin promotes a decrease in immune cell infiltration through a defect in exosome secretion. Taken together, our results provide the first evidence that oncogenic ß-catenin plays a key role in exosome biogenesis. Our study gives new insight into the impact of ß-catenin mutations on tumor microenvironment remodeling, which could lead to the development of new strategies to enhance immunotherapeutic response.
-
- Cell Biology
Asymmetric cell divisions (ACDs) generate two daughter cells with identical genetic information but distinct cell fates through epigenetic mechanisms. However, the process of partitioning different epigenetic information into daughter cells remains unclear. Here, we demonstrate that the nucleosome remodeling and deacetylase (NuRD) complex is asymmetrically segregated into the surviving daughter cell rather than the apoptotic one during ACDs in Caenorhabditis elegans. The absence of NuRD triggers apoptosis via the EGL-1-CED-9-CED-4-CED-3 pathway, while an ectopic gain of NuRD enables apoptotic daughter cells to survive. We identify the vacuolar H+–adenosine triphosphatase (V-ATPase) complex as a crucial regulator of NuRD’s asymmetric segregation. V-ATPase interacts with NuRD and is asymmetrically segregated into the surviving daughter cell. Inhibition of V-ATPase disrupts cytosolic pH asymmetry and NuRD asymmetry. We suggest that asymmetric segregation of V-ATPase may cause distinct acidification levels in the two daughter cells, enabling asymmetric epigenetic inheritance that specifies their respective life-versus-death fates.
