IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-59346-5.html
   My bibliography  Save this article

METTL14 regulates chondrogenesis through the GDF5–RUNX–extracellular matrix gene axis during limb development

Author

Listed:
  • Nobuko Katoku-Kikyo

    (University of Minnesota
    University of Minnesota)

  • Hiroko Kawakami

    (University of Minnesota
    University of Minnesota)

  • Max Cantor

    (University of Minnesota
    University of Minnesota)

  • Yasuhiko Kawakami

    (University of Minnesota
    University of Minnesota)

  • Nobuaki Kikyo

    (University of Minnesota
    University of Minnesota)

Abstract

m6A RNA methylation is essential for many aspects of mammalian development but its roles in chondrogenesis remain largely unknown. Here, we show that m6A is necessary for chondrogenesis and limb morphogenesis using limb progenitor-specific knockout mice of Mettl14, an essential subunit in the m6A methyltransferase complex. The knockout disrupts cartilage anlagen formation in limb buds with 11 downregulated proteins known to dysregulate chondrogenesis and shorten limb skeletons upon mutation in mice and humans. Further studies show a gene regulatory hierarchy among the 11 proteins. m6A stabilizes the transcript and increases the protein level of GDF5, a BMP family member. This activates the chondrogenic transcription factor genes Runx2 and Runx3, whose mRNAs are also stabilized by m6A. They promote the transcription of six collagen genes and two other chondrogenic genes, Ddrgk1 and Pbxip1. Thus, this study uncovers an m6A-based cascade essential for chondrogenesis during limb skeletal development.

Suggested Citation

  • Nobuko Katoku-Kikyo & Hiroko Kawakami & Max Cantor & Yasuhiko Kawakami & Nobuaki Kikyo, 2025. "METTL14 regulates chondrogenesis through the GDF5–RUNX–extracellular matrix gene axis during limb development," Nature Communications, Nature, vol. 16(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59346-5
    DOI: 10.1038/s41467-025-59346-5
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-59346-5
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-59346-5?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59346-5. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.