Tendon Cell Regeneration Is Mediated by Attachment Site-Resident Progenitors and BMP Signaling

• Published in: Current biology Vol. 30; no. 17; pp. 3277 - 3292.e5
• Main Authors: Niu, Xubo, Subramanian, Arul, Hwang, Tyler H., Schilling, Thomas F., Galloway, Jenna L.
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 07.09.2020
• Subjects: ablation; Animals; Animals, Genetically Modified - genetics; Animals, Genetically Modified - growth & development; Animals, Genetically Modified - metabolism; BMP; Bone Morphogenetic Proteins - genetics; Bone Morphogenetic Proteins - metabolism; Cell Differentiation; Musculoskeletal System - metabolism; nkx2.5; progenitor cells; Regeneration; scleraxis; sox10; Stem Cells - cytology; Stem Cells - metabolism; tendon; Tendons - cytology; zebrafish; Zebrafish - genetics; Zebrafish - growth & development; Zebrafish - metabolism; tendon; sox10; BMP; regeneration; ablation; progenitor cells; zebrafish; scleraxis; nkx2.5
• ISSN: 0960-9822; 1879-0445; 1879-0445
• DOI: 10.1016/j.cub.2020.06.016

The musculoskeletal system is a striking example of how cell identity and position is coordinated across multiple tissues to ensure function. However, it is unclear upon tissue loss, such as complete loss of cells of a central musculoskeletal connecting tendon, whether neighboring tissues harbor progenitors capable of mediating regeneration. Here, using a zebrafish model, we genetically ablate all embryonic tendon cells and find complete regeneration of tendon structure and pattern. We identify two regenerative progenitor populations, sox10+ perichondrial cells surrounding cartilage and nkx2.5+ cells surrounding muscle. Surprisingly, laser ablation of sox10+ cells, but not nkx2.5+ cells, increases tendon progenitor number in the perichondrium, suggesting a mechanism to regulate attachment location. We find BMP signaling is active in regenerating progenitor cells and is necessary and sufficient for generating new scxa+ cells. Our work shows that muscle and cartilage connective tissues harbor progenitor cells capable of fully regenerating tendons, and this process is regulated by BMP signaling. •Generation of a zebrafish tendon cell ablation line•Robust tendon cell regeneration in zebrafish•sox10+ and nkx2.5+ cells from attachment sites contribute to tendon cell regeneration•BMP signaling is sufficient and required for tendon cell regeneration Using a new tendon cell ablation model, Niu et al. show that zebrafish can fully regenerate properly patterned and structurally correct tendons. Cellular regeneration of the tendon is driven by BMP signaling and newly recruited progenitors from connective tissue surrounding cartilage and muscle, specifically at musculoskeletal attachment sites.