# Molecular Mechanisms of Myoblast Fusion

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $356,400

## Abstract

PROJECT SUMMARY
Skeletal muscle is a unique organ that is composed of multinucleate muscle fibers, each of which is the
product of fusion of hundreds or even thousands of myoblasts. Myoblast fusion is not only important for
skeletal muscle development, but also critical for satellite cell-based muscle regeneration. Despite a large body
of studies over several decades, the mechanisms underlying myoblast fusion in humans remain poorly
understood. Recent studies in the fruit fly Drosophila have begun to reveal unprecedented details about the
molecular and cellular mechanisms of myoblast fusion. The striking evolutionary conservation between fly and
mammalian myogenesis makes Drosophila a particularly relevant system to study myoblast fusion in vivo.
Recent studies from our lab have uncovered a novel cellular mechanism underlying myoblast fusion. We show
that myoblast fusion is mediated by F-actin-enriched podosome-like structure (PLS), which invades the
apposing fusion partner with multiple protrusive fingers leading to fusion pore formation. Furthermore, we have
discovered a mechanosensory response in the receiving fusion partner and demonstrated that mechanical
tension is a driving force for myoblast fusion. In this proposal, we will build upon our previous work and expand
our studies into two new directions – calcium signaling and phospholipid function in myoblast fusion. We will
use a multifaceted approach, including fly genetics, molecular biology, biochemistry, immunohistochemistry,
live imaging, super-resolution microscopy and electron microscopy, to study the mechanisms by which calcium
and PIP2 signaling regulate myoblast fusion. Given the molecular and cellular conservation of myoblast fusion
between fly and mammals, the proposed mechanistic studies using the simpler and genetically tractable
Drosophila system will lead to significant insights into human muscle biology in health and disease, and
ultimately provide a basis for developing more efficient therapeutics against the life debilitating muscle
degeneration diseases.

## Key facts

- **NIH application ID:** 9924252
- **Project number:** 5R01AR053173-14
- **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:** $356,400
- **Award type:** 5
- **Project period:** 2006-07-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9924252

## Citation

> US National Institutes of Health, RePORTER application 9924252, Molecular Mechanisms of Myoblast Fusion (5R01AR053173-14). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9924252. Licensed CC0.

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