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 Wallinghurst
  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 548
  • Annotations
Cite this article as: eLife 2021;10:e63556 doi: 10.7554/eLife.63556

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.

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 Wallinghurst

    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

  • 548
    Page views
  • 92
    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
    2. Neuroscience

    Robo recruitment of the Wave Regulatory Complex plays an essential and conserved role in midline repulsion

    Karina Chaudhari et al.
    Research Article

    The Roundabout (Robo) guidance receptor family induces axon repulsion in response to its ligand Slit by inducing local cytoskeletal changes; however, the link to the cytoskeleton and the nature of these cytoskeletal changes are poorly understood. Here, we show that the heteropentameric Scar/Wave Regulatory Complex (WRC) which drives Arp2/3-induced branched actin polymerization, is a direct effector of Robo signaling. Biochemical evidence shows that Slit triggers WRC recruitment to the Robo receptor's WIRS motif. In Drosophila embryos, mutants of the WRC enhance Robo1-dependent midline crossing defects. Additionally, mutating Robo1's WIRS motif significantly reduces receptor activity in rescue assays in vivo, and CRISPR-Cas9 mutagenesis shows that the WIRS motif is essential for endogenous Robo1 function. Finally, axon guidance assays in mouse dorsal spinal commissural axons and gain-of-function experiments in chick embryos demonstrate that the WIRS motif is also required for Robo1 repulsion in mammals. Together, our data support an essential conserved role for the WIRS-WRC interaction in Robo1-mediated axon repulsion.

    1. Developmental Biology

    In vivo proximity labeling identifies cardiomyocyte protein networks during zebrafish heart regeneration

    Mira I Pronobis et al.
    Tools and Resources Updated

    Strategies have not been available until recently to uncover interacting protein networks specific to key cell types, their subcellular compartments, and their major regulators during complex in vivo events. Here, we apply BioID2 proximity labeling to capture protein networks acting within cardiomyocytes during a key model of innate heart regeneration in zebrafish. Transgenic zebrafish expressing a promiscuous BirA2 localized to the entire myocardial cell or membrane compartment were generated, each identifying distinct proteomes in adult cardiomyocytes that became altered during regeneration. BioID2 profiling for interactors with ErbB2, a co-receptor for the cardiomyocyte mitogen Nrg1, implicated Rho A as a target of ErbB2 signaling in cardiomyocytes. Blockade of Rho A during heart regeneration, or during cardiogenic stimulation by the mitogenic influences Nrg1, Vegfaa, or vitamin D, disrupted muscle creation. Our findings reveal proximity labeling as a useful resource to interrogate cell proteomes and signaling networks during tissue regeneration in zebrafish.

    1. Cell Biology
    2. Developmental Biology

    The recycling endosome protein Rab25 coordinates collective cell movements in the zebrafish surface epithelium

    Patrick Morley Willoughby et al.
    Research Article Updated

    In emerging epithelial tissues, cells undergo dramatic rearrangements to promote tissue shape changes. Dividing cells remain interconnected via transient cytokinetic bridges. Bridges are cleaved during abscission and currently, the consequences of disrupting abscission in developing epithelia are not well understood. We show that the Rab GTPase Rab25 localizes near cytokinetic midbodies and likely coordinates abscission through endomembrane trafficking in the epithelium of the zebrafish gastrula during epiboly. In maternal-zygotic Rab25a and Rab25b mutant embryos, morphogenic activity tears open persistent apical cytokinetic bridges that failed to undergo timely abscission. Cytokinesis defects result in anisotropic cell morphologies that are associated with a reduction of contractile actomyosin networks. This slows cell rearrangements and alters the viscoelastic responses of the tissue, all of which likely contribute to delayed epiboly. We present a model in which Rab25 trafficking coordinates cytokinetic bridge abscission and cortical actin density, impacting local cell shape changes and tissue-scale forces.