The alternative regenerative strategy of bearded dragon unveils the key processes underlying vertebrate tooth renewal

  1. Lotta Salomies
  2. Julia Eymann
  3. Imran Khan
  4. Nicolas Di-Poi  Is a corresponding author
  1. University of Helsinki, Finland

Abstract

Deep understanding of tooth regeneration is hampered by the lack of lifelong replacing oral dentition in most conventional models. Here, we show that the bearded dragon, one of the rare vertebrate species with both polyphyodont and monophyodont teeth, constitutes a key model for filling this gap, allowing direct comparison of extreme dentition types. Our developmental and high-throughput transcriptomic data of microdissected dental cells unveils the critical importance of successional dental lamina patterning, in addition to maintenance, for vertebrate tooth renewal. This patterning process happens at various levels, including directional growth but also gene expression levels, dynamics, and regionalization, and involves a large number of yet uncharacterized dental genes. Furthermore, the alternative renewal mechanism of bearded dragon dentition, with dual location of slow-cycling cells, demonstrates the importance of cell migration and functional specialization of putative epithelial stem/progenitor niches in tissue regeneration, while expanding the diversity of dental replacement strategies in vertebrates.

Data availability

All Illumina reads have been deposited on Dryad Digital Repository under the link https://datadryad.org/review?doi=doi:10.5061/dryad.k66jn2s. Primers used for qPCR and ISH probes are available in the Key Resources Table. All other data generated or analyzed during this study are included in the manuscript and Supplementary File 1.

The following data sets were generated

Article and author information

Author details

  1. Lotta Salomies

    Institute of Biotechnology, University of Helsinki, Helsinki, Finland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1518-153X
  2. Julia Eymann

    Institute of Biotechnology, University of Helsinki, Helsinki, Finland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8147-9161
  3. Imran Khan

    Institute of Biotechnology, University of Helsinki, Helsinki, Finland
    Competing interests
    The authors declare that no competing interests exist.
  4. Nicolas Di-Poi

    Institute of Biotechnology, University of Helsinki, Helsinki, Finland
    For correspondence
    nicolas.di-poi@helsinki.fi
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3313-3016

Funding

Suomen Akatemia

  • Nicolas Di-Poi

Suomen Akatemia

  • Imran Khan

Integrative Life Science Doctoral Program

  • Lotta Salomies

Helsingin Yliopisto

  • Nicolas Di-Poi

Biocemtrum Helsinki

  • Nicolas Di-Poi

Institute of biotechnology

  • Nicolas Di-Poi

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 reptile captive breedings and experiments were approved by the Laboratory Animal Centre (LAC) of the University of Helsinki and/or the National Animal Experiment Board (ELLA) in Finland (license numbers ESLH-2007-07445/ym-23, ESAVI/7484/04.10.07/2016, and ESAVI/13139/04.10.05/2017).

Reviewing Editor

  1. Karen E Sears, University of California, Los Angeles, United States

Version history

  1. Received: April 15, 2019
  2. Accepted: August 16, 2019
  3. Accepted Manuscript published: August 16, 2019 (version 1)
  4. Version of Record published: September 13, 2019 (version 2)

Copyright

© 2019, Salomies 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

  • 3,741
    Page views
  • 283
    Downloads
  • 21
    Citations

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

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. Lotta Salomies
  2. Julia Eymann
  3. Imran Khan
  4. Nicolas Di-Poi
(2019)
The alternative regenerative strategy of bearded dragon unveils the key processes underlying vertebrate tooth renewal
eLife 8:e47702.
https://doi.org/10.7554/eLife.47702

Further reading

    1. Chromosomes and Gene Expression
    2. Developmental Biology
    Virginia L Pimmett, Mounia Lagha
    Insight

    Imaging experiments reveal the complex and dynamic nature of the transcriptional hubs associated with Notch signaling.

    1. Cell Biology
    2. Developmental Biology
    Simon Schneider, Andjela Kovacevic ... Hubert Schorle
    Research Article

    Cylicins are testis-specific proteins, which are exclusively expressed during spermiogenesis. In mice and humans, two Cylicins, the gonosomal X-linked Cylicin 1 (Cylc1/CYLC1) and the autosomal Cylicin 2 (Cylc2/CYLC2) genes, have been identified. Cylicins are cytoskeletal proteins with an overall positive charge due to lysine-rich repeats. While Cylicins have been localized in the acrosomal region of round spermatids, they resemble a major component of the calyx within the perinuclear theca at the posterior part of mature sperm nuclei. However, the role of Cylicins during spermiogenesis has not yet been investigated. Here, we applied CRISPR/Cas9-mediated gene editing in zygotes to establish Cylc1- and Cylc2-deficient mouse lines as a model to study the function of these proteins. Cylc1 deficiency resulted in male subfertility, whereas Cylc2-/-, Cylc1-/yCylc2+/-, and Cylc1-/yCylc2-/- males were infertile. Phenotypical characterization revealed that loss of Cylicins prevents proper calyx assembly during spermiogenesis. This results in decreased epididymal sperm counts, impaired shedding of excess cytoplasm, and severe structural malformations, ultimately resulting in impaired sperm motility. Furthermore, exome sequencing identified an infertile man with a hemizygous variant in CYLC1 and a heterozygous variant in CYLC2, displaying morphological abnormalities of the sperm including the absence of the acrosome. Thus, our study highlights the relevance and importance of Cylicins for spermiogenic remodeling and male fertility in human and mouse, and provides the basis for further studies on unraveling the complex molecular interactions between perinuclear theca proteins required during spermiogenesis.