Transcriptome profiling of tendon fibroblasts at the onset of embryonic muscle contraction reveals novel force-responsive genes
- University of California, Irvine, United States
Abstract
Mechanical forces play a critical role in tendon development and function, influencing cell behavior through mechanotransduction signaling pathways and subsequent extracellular matrix (ECM) remodeling. Here we investigate the molecular mechanisms by which tenocytes in developing zebrafish embryos respond to muscle contraction forces during the onset of swimming and cranial muscle activity. Using genome-wide bulk RNA sequencing of FAC-sorted tenocytes we identify novel tenocyte markers and genes involved in tendon mechanotransduction. Embryonic tendons show dramatic changes in expression of matrix remodeling associated 5b (mxra5b), matrilin1 (matn1), and the transcription factor kruppel-like factor 2a (klf2a), as muscles start to contract. Using embryos paralyzed either by loss of muscle contractility or neuromuscular stimulation we confirm that muscle contractile forces influence the spatial and temporal expression patterns of all three genes. Quantification of these gene expression changes across tenocytes at multiple tendon entheses and myotendinous junctions reveals that their responses depend on force intensity, duration and tissue stiffness. These force-dependent feedback mechanisms in tendons, particularly in the ECM, have important implications for improved treatments of tendon injuries and atrophy.
Data availability
We have uploaded our datasets, software code etc to the GEO portal. We have received the GEO accession numbers for the datasets - GSE292682 and GSE292683All source data (quantification data) has been uploaded with the manuscript and referred to in the figure legends respectively.
Article and author information
Author details
Thomas F Schilling
Funding
National Science Foundation (MCB2028424)
- Thomas F Schilling
National Institutes of Health (R01 DE13828)
- Thomas F Schilling
National Institutes of Health (R01 DE30565)
- Thomas F Schilling
National Institutes of Health (R01 AR67797)
- Thomas F Schilling
National Science Foundation- Simons Center for Multiscale Cell Fate (594598)
- Pavan K Nayak
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
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 (#AUP-23-099) of the University of California Irvine. The protocol was approved by the UCI IACUC Committee and ULAR (University Laboratory Animal Welfare).
Copyright
© 2025, Nayak et al.
This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
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Transcriptome profiling of tendon fibroblasts at the onset of embryonic muscle contraction reveals novel force-responsive genes
eLife 14:e105802.
https://doi.org/10.7554/eLife.105802
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