Extracellular matrix deposition precedes muscle-tendon integration during murine forelimb morphogenesis

Abstract The development of a functional musculoskeletal system requires the combination of contractile muscle and extracellular matrix (ECM)-rich tendons that transmit muscle-generated force to bone. Despite the different embryologic origins, muscle and tendon integrate at the myotendinous junction...

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Main Authors: Yue Leng, Sarah N. Lipp, Ye Bu, Hannah Larson, Kathryn R. Jacobson, Haley A. Colling, Sarah Calve
Format: Article
Language:English
Published: Nature Portfolio 2025-08-01
Series:Communications Biology
Online Access:https://doi.org/10.1038/s42003-025-08653-0
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author Yue Leng
Sarah N. Lipp
Ye Bu
Hannah Larson
Kathryn R. Jacobson
Haley A. Colling
Sarah Calve
author_facet Yue Leng
Sarah N. Lipp
Ye Bu
Hannah Larson
Kathryn R. Jacobson
Haley A. Colling
Sarah Calve
author_sort Yue Leng
collection DOAJ
description Abstract The development of a functional musculoskeletal system requires the combination of contractile muscle and extracellular matrix (ECM)-rich tendons that transmit muscle-generated force to bone. Despite the different embryologic origins, muscle and tendon integrate at the myotendinous junction (MTJ) to connect across this interface. While the cell-cell signaling factors have received considerable attention, how the ECM links these tissues remains unclear. Here, we show the 3D distribution of ECM during forelimb development in wildtype (WT) and muscle-less Pax3 Cre/Cre mice. At E12, prior to MTJ integration, an aligned ECM is present at the presumptive insertion of the long triceps into the ulna. Tendon-like and muscle compartmentalization structures still form when muscle is knocked out; however, MTJ-specific ECM is not observed when muscle is absent. Our results show that the architecture of the muscle-tendon unit is established independent of muscle, but muscle is needed for the proper assembly of ECM at the MTJ.
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institution Kabale University
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spelling doaj-art-3be7981f729949e38432c6d79ea0e7142025-08-20T03:46:21ZengNature PortfolioCommunications Biology2399-36422025-08-018111210.1038/s42003-025-08653-0Extracellular matrix deposition precedes muscle-tendon integration during murine forelimb morphogenesisYue Leng0Sarah N. Lipp1Ye Bu2Hannah Larson3Kathryn R. Jacobson4Haley A. Colling5Sarah Calve6Weldon School of Biomedical Engineering, Purdue UniversityWeldon School of Biomedical Engineering, Purdue UniversityWeldon School of Biomedical Engineering, Purdue UniversityPaul M. Rady Department of Mechanical Engineering, University of Colorado BoulderPurdue University Interdisciplinary Life Science ProgramDepartment of Integrative Physiology, University of Colorado BoulderWeldon School of Biomedical Engineering, Purdue UniversityAbstract The development of a functional musculoskeletal system requires the combination of contractile muscle and extracellular matrix (ECM)-rich tendons that transmit muscle-generated force to bone. Despite the different embryologic origins, muscle and tendon integrate at the myotendinous junction (MTJ) to connect across this interface. While the cell-cell signaling factors have received considerable attention, how the ECM links these tissues remains unclear. Here, we show the 3D distribution of ECM during forelimb development in wildtype (WT) and muscle-less Pax3 Cre/Cre mice. At E12, prior to MTJ integration, an aligned ECM is present at the presumptive insertion of the long triceps into the ulna. Tendon-like and muscle compartmentalization structures still form when muscle is knocked out; however, MTJ-specific ECM is not observed when muscle is absent. Our results show that the architecture of the muscle-tendon unit is established independent of muscle, but muscle is needed for the proper assembly of ECM at the MTJ.https://doi.org/10.1038/s42003-025-08653-0
spellingShingle Yue Leng
Sarah N. Lipp
Ye Bu
Hannah Larson
Kathryn R. Jacobson
Haley A. Colling
Sarah Calve
Extracellular matrix deposition precedes muscle-tendon integration during murine forelimb morphogenesis
Communications Biology
title Extracellular matrix deposition precedes muscle-tendon integration during murine forelimb morphogenesis
title_full Extracellular matrix deposition precedes muscle-tendon integration during murine forelimb morphogenesis
title_fullStr Extracellular matrix deposition precedes muscle-tendon integration during murine forelimb morphogenesis
title_full_unstemmed Extracellular matrix deposition precedes muscle-tendon integration during murine forelimb morphogenesis
title_short Extracellular matrix deposition precedes muscle-tendon integration during murine forelimb morphogenesis
title_sort extracellular matrix deposition precedes muscle tendon integration during murine forelimb morphogenesis
url https://doi.org/10.1038/s42003-025-08653-0
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AT hannahlarson extracellularmatrixdepositionprecedesmuscletendonintegrationduringmurineforelimbmorphogenesis
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