Transcriptome profiling of tendon fibroblasts at the onset of embryonic muscle contraction reveals novel force-responsive genes
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 r...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2025-03-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/105802 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850139813996396544 |
|---|---|
| author | Pavan K Nayak Arul Subramanian Thomas F Schilling |
| author_facet | Pavan K Nayak Arul Subramanian Thomas F Schilling |
| author_sort | Pavan K Nayak |
| collection | DOAJ |
| description | 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), matrilin 1 (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. |
| format | Article |
| id | doaj-art-9c4c48bd2451406abbf5494990e1b5fb |
| institution | OA Journals |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-03-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj-art-9c4c48bd2451406abbf5494990e1b5fb2025-08-20T02:30:06ZengeLife Sciences Publications LtdeLife2050-084X2025-03-011410.7554/eLife.105802Transcriptome profiling of tendon fibroblasts at the onset of embryonic muscle contraction reveals novel force-responsive genesPavan K Nayak0https://orcid.org/0000-0002-4360-6729Arul Subramanian1https://orcid.org/0000-0001-8455-6804Thomas F Schilling2https://orcid.org/0000-0003-1798-8695Department of Developmental and Cell Biology, University of California, Irvine, United StatesDepartment of Developmental and Cell Biology, University of California, Irvine, United StatesDepartment of Developmental and Cell Biology, University of California, Irvine, United StatesMechanical 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), matrilin 1 (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.https://elifesciences.org/articles/105802tendon developmentextracellular matrixmechanotransductiontranscriptional regulationenthesismyotendinous junction |
| spellingShingle | Pavan K Nayak Arul Subramanian Thomas F Schilling Transcriptome profiling of tendon fibroblasts at the onset of embryonic muscle contraction reveals novel force-responsive genes eLife tendon development extracellular matrix mechanotransduction transcriptional regulation enthesis myotendinous junction |
| title | Transcriptome profiling of tendon fibroblasts at the onset of embryonic muscle contraction reveals novel force-responsive genes |
| title_full | Transcriptome profiling of tendon fibroblasts at the onset of embryonic muscle contraction reveals novel force-responsive genes |
| title_fullStr | Transcriptome profiling of tendon fibroblasts at the onset of embryonic muscle contraction reveals novel force-responsive genes |
| title_full_unstemmed | Transcriptome profiling of tendon fibroblasts at the onset of embryonic muscle contraction reveals novel force-responsive genes |
| title_short | Transcriptome profiling of tendon fibroblasts at the onset of embryonic muscle contraction reveals novel force-responsive genes |
| title_sort | transcriptome profiling of tendon fibroblasts at the onset of embryonic muscle contraction reveals novel force responsive genes |
| topic | tendon development extracellular matrix mechanotransduction transcriptional regulation enthesis myotendinous junction |
| url | https://elifesciences.org/articles/105802 |
| work_keys_str_mv | AT pavanknayak transcriptomeprofilingoftendonfibroblastsattheonsetofembryonicmusclecontractionrevealsnovelforceresponsivegenes AT arulsubramanian transcriptomeprofilingoftendonfibroblastsattheonsetofembryonicmusclecontractionrevealsnovelforceresponsivegenes AT thomasfschilling transcriptomeprofilingoftendonfibroblastsattheonsetofembryonicmusclecontractionrevealsnovelforceresponsivegenes |