1. Developmental Biology
Download icon

Deficient spermiogenesis in mice lacking Rlim

  1. Feng Wang
  2. Maria Gracia Gervasi
  3. Ana Bošković
  4. Fengyun Sun
  5. Vera D Rinaldi
  6. Jun Yu
  7. Mary C Wallingford
  8. Darya A Tourzani
  9. Jesse Mager
  10. Lihua J Zhu
  11. Oliver J Rando
  12. Pablo E Visconti
  13. Lara Strittmatter
  14. Ingolf Bach  Is a corresponding author
  1. University of Massachusetts Medical School, United States
  2. University of Massachusetts Amherst, United States
Research Article
  • Cited 0
  • Views 618
  • Annotations
Cite this article as: eLife 2021;10:e63556 doi: 10.7554/eLife.63556
Voice your concerns about research culture and research communication: Have your say in our 7th annual survey.
Take the Survey

Abstract

The X-linked gene Rlim plays major roles in female mouse development and reproduction, where it is crucial for the maintenance of imprinted X chromosome inactivation in extraembryonic tissues of embryos. However, while females carrying a systemic Rlim knockout (KO) die around implantation, male Rlim KO mice appear healthy and are fertile. Here we report an important role for Rlim in testis where it is highly expressed in post-meiotic round spermatids as well as in Sertoli cells. Systemic deletion of the Rlim gene results in lower numbers of mature sperm that contains excess cytoplasm, leading to decreased sperm motility and in vitro fertilization rates. Targeting the conditional Rlim cKO specifically to the spermatogenic cell lineage largely recapitulates this phenotype. These results reveal functions of Rlim in male reproduction specifically in round spermatids during spermiogenesis.

Data availability

RNAseq data have been deposited in GEO under accession code GSE114593.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Feng Wang

    Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Maria Gracia Gervasi

    Department of Veterinary and Animal Science, University of Massachusetts Amherst, Amherst, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Ana Bošković

    Biochemistry, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Fengyun Sun

    Department of Biochemistry, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Vera D Rinaldi

    Department of Biochemistry, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0051-1754

  6. Jun Yu

    Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.

  7. Mary C Wallingford

    Dept of Veterinary & Animal Sciences, University of Massachusetts Amherst, Amherst, United States
    Competing interests
    The authors declare that no competing interests exist.

  8. Darya A Tourzani

    Dept of Veterinary & Animal Sciences, University of Massachusetts Amherst, Amherst, United States
    Competing interests
    The authors declare that no competing interests exist.

  9. Jesse Mager

    Dept of Veterinary & Animal Sciences, University of Massachusetts Amherst, Amherst, United States
    Competing interests
    The authors declare that no competing interests exist.

  10. Lihua J Zhu

    Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.

  11. Oliver J Rando

    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1516-9397

  12. Pablo E Visconti

    Dept of Veterinary & Animal Sciences, University of Massachusetts Amherst, Amherst, United States
    Competing interests
    The authors declare that no competing interests exist.

  13. Lara Strittmatter

    Electron microscopy core, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.

  14. Ingolf Bach

    Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, United States
    For correspondence
    ingolf.bach@umassmed.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4505-8946

Funding

National Institutes of Health (GM128168)

  • Ingolf Bach

National Institutes of Health (HD080224)

  • Oliver J Rando

National Institutes of Health (HD38082)

  • Pablo E Visconti

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

Ethics

Animal experimentation: All mice were housed in the animal facility of UMMS and utilized according to NIH guidelines and those established by the UMMS Institute of Animal Care and Usage Committee (IACUC; protocol #201900344).

Reviewing Editor

  1. Jeannie T Lee, Massachusetts General Hospital, United States

Publication history

  1. Received: September 29, 2020
  2. Accepted: February 22, 2021
  3. Accepted Manuscript published: February 23, 2021 (version 1)
  4. Accepted Manuscript updated: February 24, 2021 (version 2)
  5. Version of Record published: March 5, 2021 (version 3)

Copyright

© 2021, Wang 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

  • 618
    Page views
  • 98
    Downloads
  • 0
    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)

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

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

Categories and tags

Research organism

Further reading

    1. Developmental Biology

    Ongoing repair of migration-coupled DNA damage allows planarian adult stem cells to reach wound sites

    Sounak Sahu et al.
    Short Report Updated

    Mechanical stress during cell migration may be a previously unappreciated source of genome instability, but the extent to which this happens in any animal in vivo remains unknown. We consider an in vivo system where the adult stem cells of planarian flatworms are required to migrate to a distal wound site. We observe a relationship between adult stem cell migration and ongoing DNA damage and repair during tissue regeneration. Migrating planarian stem cells undergo changes in nuclear shape and exhibit increased levels of DNA damage. Increased DNA damage levels reduce once stem cells reach the wound site. Stem cells in which DNA damage is induced prior to wounding take longer to initiate migration and migrating stem cell populations are more sensitive to further DNA damage than stationary stem cells. RNAi-mediated knockdown of DNA repair pathway components blocks normal stem cell migration, confirming that active DNA repair pathways are required to allow successful migration to a distal wound site. Together these findings provide evidence that levels of migration-coupled-DNA-damage are significant in adult stem cells and that ongoing migration requires DNA repair mechanisms. Our findings reveal that migration of normal stem cells in vivo represents an unappreciated source of damage, which could be a significant source of mutations in animals during development or during long-term tissue homeostasis.

    1. Developmental Biology
    2. Plant Biology

    Organ geometry channels reproductive cell fate in the Arabidopsis ovule primordium

    Elvira Hernandez-Lagana et al.
    Research Article

    In multicellular organisms, sexual reproduction requires the separation of the germline from the soma. In flowering plants, the female germline precursor differentiates as a single spore mother cell (SMC) as the ovule primordium forms. Here, we explored how organ growth contributes to SMC differentiation. We generated 92 annotated 3D images at cellular resolution in Arabidopsis. We identified the spatio-temporal pattern of cell division that acts in a domain-specific manner as the primordium forms. Tissue growth models uncovered plausible morphogenetic principles involving a spatially confined growth signal, differential mechanical properties, and cell growth anisotropy. Our analysis revealed that SMC characteristics first arise in more than one cell but SMC fate becomes progressively restricted to a single cell during organ growth. Altered primordium geometry coincided with a delay in the fate restriction process in katanin mutants. Altogether, our study suggests that tissue geometry channels reproductive cell fate in the Arabidopsis ovule primordium.

    1. Cancer Biology
    2. Developmental Biology

    An NKX2-1/ERK/WNT feedback loop modulates gastric identity and response to targeted therapy in lung adenocarcinoma

    Rediet Zewdu et al.
    Research Article Updated

    Cancer cells undergo lineage switching during natural progression and in response to therapy. NKX2-1 loss in human and murine lung adenocarcinoma leads to invasive mucinous adenocarcinoma (IMA), a lung cancer subtype that exhibits gastric differentiation and harbors a distinct spectrum of driver oncogenes. In murine BRAFV600E-driven lung adenocarcinoma, NKX2-1 is required for early tumorigenesis, but dispensable for established tumor growth. NKX2-1-deficient, BRAFV600E-driven tumors resemble human IMA and exhibit a distinct response to BRAF/MEK inhibitors. Whereas BRAF/MEK inhibitors drive NKX2-1-positive tumor cells into quiescence, NKX2-1-negative cells fail to exit the cell cycle after the same therapy. BRAF/MEK inhibitors induce cell identity switching in NKX2-1-negative lung tumors within the gastric lineage, which is driven in part by WNT signaling and FoxA1/2. These data elucidate a complex, reciprocal relationship between lineage specifiers and oncogenic signaling pathways in the regulation of lung adenocarcinoma identity that is likely to impact lineage-specific therapeutic strategies.