1. Cell Biology

Specific deletion of Axin1 leads to activation of β-catenin/BMP signaling resulting in fibular hemimelia phenotype in mice

  1. Rong Xie
  2. Dan Yi
  3. Daofu Zeng
  4. Qiang Jie
  5. Qinglin Kang
  6. Zeng Zhang
  7. Zhenlin Zhang
  8. Guozhi Xiao
  9. Lin Chen
  10. Liping Tong  Is a corresponding author
  11. Di Chen  Is a corresponding author
  1. Rush University Medical Center, United States
  2. Chinese Academy of Sciences, China
  3. Xi'an Jiaotong University, China
  4. Shanghai JiaoTong University, China
  5. Southern University of Science and Technology, China
  6. Army Medical University, China
https://doi.org/10.7554/eLife.80013
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Cite this article
  1. Rong Xie
  2. Dan Yi
  3. Daofu Zeng
  4. Qiang Jie
  5. Qinglin Kang
  6. Zeng Zhang
  7. Zhenlin Zhang
  8. Guozhi Xiao
  9. Lin Chen
  10. Liping Tong
  11. Di Chen
(2022)
Specific deletion of Axin1 leads to activation of β-catenin/BMP signaling resulting in fibular hemimelia phenotype in mice
eLife 11:e80013.
https://doi.org/10.7554/eLife.80013
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Abstract

Axin1 is a key regulator of canonical Wnt signaling pathway. Roles of Axin1 in skeletal development and in disease occurrence have not been fully defined. Here, we report that Axin1 is essential for lower limb development. Specific deletion of Axin1 in limb mesenchymal cells leads to fibular hemimelia (FH)-like phenotype, associated with tarsal coalition. Further studies demonstrate that FH disease is associated with additional defects in Axin1 knockout (KO) mice, including decreased osteoclast formation and defects in angiogenesis. We then provide in vivo evidence showing that Axin1 controls limb development through both canonical β-catenin and BMP signaling pathways. We demonstrate that inhibition of β-catenin or BMP signaling could significantly reverse the FH phenotype in mice. Together, our findings reveal that integration of β-catenin and BMP signaling by Axin1 is required for lower limb development. Defect in Axin1 signaling could lead to the development of FH disease.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting file; Source Data files have been provided for Figures.

Article and author information

Author details

  1. Rong Xie

    Department of Orthopedic Surgery, Rush University Medical Center, Chicago, United States
    Competing interests
    No competing interests declared.

  2. Dan Yi

    Research Center for Computer-aided Drug Discovery, Chinese Academy of Sciences, Shenzhen, China
    Competing interests
    No competing interests declared.

  3. Daofu Zeng

    Research Center for Computer-aided Drug Discovery, Chinese Academy of Sciences, Shenzhen, China
    Competing interests
    No competing interests declared.

  4. Qiang Jie

    Department of Orthopedic Surgery, Xi'an Jiaotong University, Xi'an, China
    Competing interests
    No competing interests declared.

  5. Qinglin Kang

    Department of Orthopedic Surgery, Shanghai JiaoTong University, Shanghai, China
    Competing interests
    No competing interests declared.

  6. Zeng Zhang

    Department of Orthopedic Surgery, Shanghai JiaoTong University, Shanghai, China
    Competing interests
    No competing interests declared.

  7. Zhenlin Zhang

    Department of Osteoporosis and Bone Diseases, Shanghai JiaoTong University, Shanghai, China
    Competing interests
    No competing interests declared.

  8. Guozhi Xiao

    Southern University of Science and Technology, Shenzhen, China
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4269-2450

  9. Lin Chen

    Department of Wound Repair and Rehabilitation, Army Medical University, Chongqing, China
    Competing interests
    No competing interests declared.

  10. Liping Tong

    Research Center for Computer-aided Drug Discovery, Chinese Academy of Sciences, Shenzhen, China
    For correspondence
    lp.tong@siat.ac.cn
    Competing interests
    No competing interests declared.

  11. Di Chen

    Research Center for Computer-aided Drug Discovery, Chinese Academy of Sciences, Shenzhen, China
    For correspondence
    di.chen@siat.ac.cn
    Competing interests
    Di Chen, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4258-3457

Funding

National Natural Science Foundation of China (82030067)

  • Di Chen

National Natural Science Foundation of China (82161160342)

  • Di Chen

National Natural Science Foundation of China (82172397)

  • Liping Tong

National Natural Science Foundation of China (81974320)

  • Zhenlin Zhang

National Key Research and Development Program of China (2021YFB3800800)

  • Di Chen

National Key Research and Development Program of China (2021YFB3800800)

  • Liping Tong

Guangdong Basic and Applied Basic Research Foundation (2021A1515111075)

  • Dan Yi

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

Reviewing Editor

  1. Xu Cao, Johns Hopkins University, United States

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (SIAT-IACUC-200302-YYS-CD-A1063) of the Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences.

Version history

  1. Received: May 5, 2022
  2. Preprint posted: July 5, 2022 (view preprint)
  3. Accepted: December 20, 2022
  4. Accepted Manuscript published: December 21, 2022 (version 1)
  5. Version of Record published: January 5, 2023 (version 2)

Copyright

© 2022, Xie 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. Rong Xie
  2. Dan Yi
  3. Daofu Zeng
  4. Qiang Jie
  5. Qinglin Kang
  6. Zeng Zhang
  7. Zhenlin Zhang
  8. Guozhi Xiao
  9. Lin Chen
  10. Liping Tong
  11. Di Chen
(2022)
Specific deletion of Axin1 leads to activation of β-catenin/BMP signaling resulting in fibular hemimelia phenotype in mice
eLife 11:e80013.
https://doi.org/10.7554/eLife.80013

Share this article

https://doi.org/10.7554/eLife.80013

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