Species-specific sensitivity to TGFβ signaling and changes to the Mmp13 promoter underlie avian jaw development and evolution

  1. Spenser S Smith
  2. Daniel Chu
  3. Tiange Qu
  4. Jessye A Aggleton
  5. Richard A Schneider  Is a corresponding author
  1. University of California, San Francisco, United States

Abstract

Precise developmental control of jaw length is critical for survival, but underlying molecular mechanisms remain poorly understood. The jaw skeleton arises from neural crest mesenchyme (NCM), and we previously demonstrated that these progenitor cells express more bone-resorbing enzymes including Matrix metalloproteinase 13 (Mmp13) when they generate shorter jaws in quail embryos versus longer jaws in duck. Moreover, if we inhibit bone resorption or Mmp13, we can increase jaw length. In the current study, we uncover mechanisms establishing species-specific levels of Mmp13 and bone resorption. Quail show greater activation of, and sensitivity to Transforming Growth Factor-Beta (TGFβ) signaling than duck; where mediators like SMADs and targets like Runx2, which bind Mmp13, become elevated. Inhibiting TGFβ signaling decreases bone resorption and overexpressing Mmp13 in NCM shortens the duck lower jaw. To elucidate the basis for this differential regulation we examine the Mmp13 promoter. We discover a SMAD binding element and single nucleotide polymorphisms (SNPs) near a RUNX2 binding element that distinguish quail from duck. Altering the SMAD site and switching the SNPs abolishes TGFβ-sensitivity in the quail Mmp13 promoter but makes the duck promoter responsive. Thus, differential regulation of TGFβ signaling and Mmp13 promoter structure underlie avian jaw development and evolution.

Data availability

Data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 2, 3, 4, and 5.GenBank accession numbers for nucleotide sequences are as follows: Runx2 (MW036689) and Mmp13 (MW036690).Plasmids are also available at Addgene (https://www.addgene.org/Richard_Schneider/) subject to the terms of the original licenses under which they were obtained.

Article and author information

Author details

  1. Spenser S Smith

    Department of Orthopaedic Surgery, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Daniel Chu

    Department of Orthopaedic Surgery, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Tiange Qu

    Department of Orthopaedic Surgery, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Jessye A Aggleton

    Department of Orthopaedic Surgery, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Richard A Schneider

    Department of Orthopaedic Surgery, University of California, San Francisco, San Francisco, United States
    For correspondence
    rich.schneider@ucsf.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2626-3111

Funding

National Institutes of Health (R01 DE016402)

  • Richard A Schneider

National Institutes of Health (R01 DE025668)

  • Richard A Schneider

National Institutes of Health (S10 OD021664)

  • Richard A Schneider

National Institutes of Health (F31 DE027283)

  • Spenser S Smith

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

Reviewing Editor

  1. Marianne E Bronner, California Institute of Technology, United States

Ethics

Animal experimentation: For all experiments, we adhered to accepted practices for the humane treatment of avian embryos as described in S3.4.4 of the AVMA Guidelines for the Euthanasia of Animals: 2013 Edition (Leary et al., 2013).

Version history

  1. Received: December 22, 2020
  2. Preprint posted: December 23, 2020 (view preprint)
  3. Accepted: June 3, 2022
  4. Accepted Manuscript published: June 6, 2022 (version 1)
  5. Version of Record published: June 30, 2022 (version 2)

Copyright

© 2022, Smith 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. Spenser S Smith
  2. Daniel Chu
  3. Tiange Qu
  4. Jessye A Aggleton
  5. Richard A Schneider
(2022)
Species-specific sensitivity to TGFβ signaling and changes to the Mmp13 promoter underlie avian jaw development and evolution
eLife 11:e66005.
https://doi.org/10.7554/eLife.66005

Share this article

https://doi.org/10.7554/eLife.66005

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