# Myonuclear homeostasis in craniofacial muscles

> **NIH NIH R01** · EMORY UNIVERSITY · 2020 · $343,200

## Abstract

Project Summary/Abstract
Dysphagia is a difficulty in swallowing which is observed in 20% of the elderly and several forms of muscular
dystrophy patients and causes malnutrition and potential life threatening effects such as choking or
pneumonia by aspiration of food; however, no cure or therapeutic treatment exists. Tongue and pharyngeal
muscles are essential for proper swallowing and prevention of food/water aspiration into the lungs yet the
cellular mechanisms that underlie changes in tongue and pharyngeal muscle function with age and with
diseases, such as oculopharyngeal muscular dystrophy (OPMD), are unknown. OPMD is a late-onset,
autosomal dominant muscle disease with prominent dysfunction of the eyelid, tongue and pharyngeal muscles;
however, little is known about the mechanisms underlying the muscle-specificity of this disease. Muscle stem
cells (satellite cells, SC) of craniofacial muscles have unique myogenic properties such as chronic high levels
of proliferation and fusion with the myofiber in the absence of injury. Despite high and constant levels of
myonuclear addition into myofibers by chronic satellite cell fusion, a constant number of myonuclei per
myofiber is maintained, implying a high level of myonuclei turnover is occurring. This unusual myonuclear
homeostasis may make craniofacial muscles more vulnerable to specific diseases and age.
 We propose 3 lines of experimentation addressing the cellular mechanisms underlying myonuclear
homeostasis of craniofacial muscles. These studies will help identify mechanisms involved in the specificity of
affected muscles in OPMD and provide potential targeted therapeutic strategies for dysphagia.
Aim 1: To compare the effect of fibroadipogenic progenitor cells (FAPs) on satellite cell fusion with myofibers
between craniofacial and limb muscles. We will determine whether muscle-specific FAP differences influence
satellite cell (SC) proliferation or differentiation at different ages in mice using assays in vitro and in vivo.
Aim 2: To quantify myonuclear turnover in craniofacial muscles and examine autophagy as a mechanism for
myonuclear turnover. We will apply BrdU labeling methods to measure myonuclear turnover of craniofacial
muscles and compare to the level of myonuclear addition with aging. Autophagy, which has a role in cellular
homeostasis, will be examined as a potential mechanism for myonuclear turnover in craniofacial muscles.
Aim 3: To determine the mechanism of impaired myonuclear addition in oculopharyngeal muscular
dystrophy (OPMD) and whether myonuclear turnover is also altered. We will test whether the intrinsic
myogenic potential of SC or the extrinsic effect of FAPs on the SCs influences impaired nuclear addition in
craniofacial muscles in OPMD. In addition, we will measure the myonuclear turnover of craniofacial muscles
in OPMD mice and determine whether augmentation of autophagy signaling affects myonuclear turnover and
pathology in OPMD.

## Key facts

- **NIH application ID:** 9980795
- **Project number:** 5R01AR071397-04
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Hyojung Choo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $343,200
- **Award type:** 5
- **Project period:** 2017-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9980795

## Citation

> US National Institutes of Health, RePORTER application 9980795, Myonuclear homeostasis in craniofacial muscles (5R01AR071397-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9980795. Licensed CC0.

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