# Mechanisms underlying tendon regeneration and attachment site pattern restoration

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2021 · $358,512

## Abstract

Galloway, Jenna L Project Summary
 Tendons make essential connections between the forming musculoskeletal tissues,
enabling coordinated movement. Disruption to the development and patterning of the
musculoskeletal system can result in skeletal malformations or contractures, a congenital
abnormality that results in constriction in the movement of joints. In adults, musculoskeletal
injuries are common among active individuals and the aging population. Tendon injuries, in
particular, are complicated by a slow and limited healing, which can pose significant mobility, pain,
and quality of life issues. Comprehensive knowledge of the molecular pathways that guide tendon
development and regeneration would have broad impact in our understanding of the etiology of
congenital defects as well as in regenerative medicine approaches to tendon injuries. This
proposal aims to use the zebrafish to understand the mechanisms underlying tendon cell
regeneration and the re-establishment of attachment site pattern. Our previous studies have
shown that zebrafish and mammalian tendons are similar in gene expression, developmental
regulation, and ultrastructural properties, making them an excellent genetic system for studying
tendon biology. We also find zebrafish have robust abilities to regenerate their tendon tissue
unlike adult mammals. Building from this novel work, we propose to use a genetic cell ablation
model to dissect the cellular and molecular mechanisms underlying tendon regeneration and the
restoration of the attachment pattern. We will identify the source of the newly regenerating tendon
cells using cell proliferation assays, genetic lineage tracing, and live imaging. Examination of BMP
Responsive Element transgenic zebrafish and functional analysis indicate BMP signaling in the
regeneration of specific attachment sites. In addition, a high-throughput chemical screen identified
compounds with tendon promoting activities and whose targets may intersect the BMP pathway.
Using chemical and genetic functional assays, we will dissect the role of BMP signaling in tendon
regeneration and the re-establishment of a specific attachment site. We will also test if the
chemicals and the pathways they target can augment the regenerative response through their
potential intersection with the BMP pathway. Our proposal combines novel tools with live imaging
and functional studies and together, this will provide unprecedented visualization of tendon cell
behaviors during regeneration. We believe these studies will add crucial insight into tendon
development and regeneration, which could impact our understanding of congenital disorders and
regenerative medicine approaches to tendon injuries.

## Key facts

- **NIH application ID:** 10061555
- **Project number:** 5R01AR074541-03
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** JENNA L GALLOWAY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $358,512
- **Award type:** 5
- **Project period:** 2018-12-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10061555

## Citation

> US National Institutes of Health, RePORTER application 10061555, Mechanisms underlying tendon regeneration and attachment site pattern restoration (5R01AR074541-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10061555. Licensed CC0.

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