# Investigating mechanisms of vertebrate myoblast fusion using zebrafish as a model

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $359,609

## Abstract

PROJECT SUMMARY
Myoblast fusion, the process in which mononucleate myoblasts fuse to form multinucleate, contractile muscle
fibers, is essential for skeletal muscle development, maintenance and regeneration. Insights into the molecular
and cellular mechanisms of myoblast fusion to date have mainly come from studies of a genetic system, the fruit
fly Drosophila. Studies in Drosophila have uncovered a handful of evolutionarily conserved regulators of
myoblast fusion, ranging from cell adhesion molecules to actin polymerization regulators to mechanical sensors.
More importantly, Drosophila studies have identified a novel cellular mechanism underlying myoblast fusion at
the site of fusion – an attacking cell aggressively invades its fusion partner using actin-propelled membrane
protrusions, whereas the receiving cell increases mechanical tension to resist the invasion, leading to cell
membrane juxtaposition, fusogen engagement and plasma membrane fusion. Besides evolutionarily conserved
fusion-promoting proteins, recent studies in zebrafish and mouse have identified a pair of vertebrate-specific
fusogenic proteins, Myomaker and Myomixer (also known as Myomerger and Minion). However, how and where
these proteins facilitate myoblast fusion is largely unknown. Compared to Drosophila studies, a major issue that
hinders the study of the mechanisms underlying vertebrate myoblast fusion is the lack of knowledge of the
precise sites of fusion. While myoblast fusion appears to occur at undefined location(s) along a broad cell-cell
contact zone in cultured mammalian myoblasts, the sites of myoblast fusion in an intact animal remain completely
unknown. Thus, it is imperative to identify the sites of fusion in vivo and provide a cellular framework upon which
future studies can be built. Zebrafish is an excellent vertebrate model to study myoblast fusion in vivo, due to the
large number of small and transparent zebrafish embryos and their rapid ex-utero development. In this proposal,
we will use zebrafish as an in vivo model to define the sites of myoblast fusion in an intact vertebrate animal with
molecular markers. In addition, we will study the localization and potential interaction between the fusogens,
Myomaker and Myomixer. Furthermore, we will explore the interaction between the fusogens and the cell
adhesion molecules and the actin cytoskeleton. Insights from the proposed studies will have a broad impact on
understanding the fundamental principles of muscle development and regeneration, and ultimately may be
exploited for the development of therapeutic strategies to optimize satellite cell-mediated muscle regeneration
in patients with muscle degenerative diseases.

## Key facts

- **NIH application ID:** 10072504
- **Project number:** 1R01AR075005-01A1
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Elizabeth H Chen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $359,609
- **Award type:** 1
- **Project period:** 2020-08-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10072504

## Citation

> US National Institutes of Health, RePORTER application 10072504, Investigating mechanisms of vertebrate myoblast fusion using zebrafish as a model (1R01AR075005-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10072504. Licensed CC0.

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