1. Cell Biology
  2. Developmental Biology

Limited column formation in the embryonic growth plate implies divergent growth mechanisms during pre- and postnatal bone development

  1. Sarah Rubin
  2. Ankit Agrawal  Is a corresponding author
  3. Anne Seewald
  4. Meng-Jia Lian
  5. Olivia Gottdenker
  6. Paul Villoutreix
  7. Adrian Baule
  8. Tomer Stern
  9. Elazar Zelzer  Is a corresponding author
  1. Weizmann Institute of Science, Israel
  2. University of Michigan-Ann Arbor, United States
  3. Aix Marseille Univ, INSERM, MMG, UMR1251, France
  4. Queen Mary University of London, United Kingdom
https://doi.org/10.7554/eLife.95289
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Cite this article
  1. Sarah Rubin
  2. Ankit Agrawal
  3. Anne Seewald
  4. Meng-Jia Lian
  5. Olivia Gottdenker
  6. Paul Villoutreix
  7. Adrian Baule
  8. Tomer Stern
  9. Elazar Zelzer
(2024)
Limited column formation in the embryonic growth plate implies divergent growth mechanisms during pre- and postnatal bone development
eLife 13:e95289.
https://doi.org/10.7554/eLife.95289
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Abstract

Chondrocyte columns, which are a hallmark of growth plate architecture, play a central role in bone elongation. Columns are formed by clonal expansion following rotation of the division plane, resulting in a stack of cells oriented parallel to the growth direction. In this work, we analyzed hundreds of Confetti multicolor clones in growth plates of mouse embryos using a pipeline comprising 3D imaging and algorithms for morphometric analysis. Surprisingly, analysis of the elevation angles between neighboring pairs of cells revealed that most cells did not display the typical stacking pattern associated with column formation, implying incomplete rotation of the division plane. Morphological analysis revealed that although embryonic clones were elongated, they formed clusters oriented perpendicular to the growth direction. Analysis of growth plates of postnatal mice revealed both complex columns, composed of ordered and disordered cell stacks, and small, disorganized clusters located in the outer edges. Finally, correlation between the temporal dynamics of the ratios between clusters and columns and between bone elongation and expansion suggests that clusters may promote expansion, whereas columns support elongation. Overall, our findings support the idea that modulations of division plane rotation of proliferating chondrocytes determines the formation of either clusters or columns, a multifunctional design that regulates morphogenesis throughout pre- and postnatal bone growth. Broadly, this work provides a new understanding of the cellular mechanisms underlying growth plate activity and bone elongation during development.

Data availability

The datasets generated and analyzed during the current study are available on Zenodo at the following links: https://doi.org/10.5281/zenodo.10440013, https://doi.org/10.5281/zenodo.10444731, https://doi.org/10.5281/zenodo.10446055, https://doi.org/10.5281/zenodo.10446092, https://doi.org/10.5281/zenodo.10446121, https://doi.org/10.5281/zenodo.10446131, https://doi.org/10.5281/zenodo.10446123, https://doi.org/10.5281/zenodo.10446145.

The following data sets were generated

Article and author information

Author details

  1. Sarah Rubin

    Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0601-8802

  2. Ankit Agrawal

    Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
    For correspondence
    ankitbioinfo@gmail.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0009-0006-1700-2397

  3. Anne Seewald

    Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4904-2063

  4. Meng-Jia Lian

    Department of Biologic and Materials and Prosthodontics, University of Michigan-Ann Arbor, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Olivia Gottdenker

    Department of Biologic and Materials and Prosthodontics, University of Michigan-Ann Arbor, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Paul Villoutreix

    Turing Center for Living Systems, Aix Marseille Univ, INSERM, MMG, UMR1251, Marseille, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6333-5735

  7. Adrian Baule

    School of Mathematical Sciences, Queen Mary University of London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  8. Tomer Stern

    Department of Biologic and Materials and Prosthodontics, University of Michigan-Ann Arbor, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.

  9. Elazar Zelzer

    Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
    For correspondence
    eli.zelzer@weizmann.ac.il
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1584-6602

Funding

Israel Science Foundation (1387/23)

  • Elazar Zelzer

Weizmann - Sagol Institute for longetivity research

  • Elazar Zelzer

Julie and Eric Borman Family Research Funds

  • Elazar Zelzer

University of Michigan School of Dentistry startup funds

  • Tomer Stern

University of Michigan Oral Health Sciences PhD program

  • Meng-Jia Lian

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 animal experiments were pre-approved by and conducted according to the guidelines of the Institutional Animal Care and Use Committee (IACUC) of the Weizmann Institute (IACUC 01750221-1 and IACUC 05700723-2). All animals used in this study had access to food and water ad libitum and were maintained under controlled humidity and temperature (45-65%, 22 {plus minus} 2{degree sign}C, respectively).

Copyright

© 2024, Rubin 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.

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  1. Sarah Rubin
  2. Ankit Agrawal
  3. Anne Seewald
  4. Meng-Jia Lian
  5. Olivia Gottdenker
  6. Paul Villoutreix
  7. Adrian Baule
  8. Tomer Stern
  9. Elazar Zelzer
(2024)
Limited column formation in the embryonic growth plate implies divergent growth mechanisms during pre- and postnatal bone development
eLife 13:e95289.
https://doi.org/10.7554/eLife.95289

Share this article

https://doi.org/10.7554/eLife.95289

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