# EphA7 promotes contact-dependent myogenesis

> **NIH NIH R01** · UNIVERSITY OF MISSOURI-COLUMBIA · 2021 · $316,812

## Abstract

SUMMARY
The conversion of proliferating skeletal muscle precursors (myoblasts) to terminally-differentiated myocytes
is a critical step in skeletal muscle development and repair; control of this process is therefore of
fundamental importance in both muscle development and muscle regeneration after injury. The tendency for
myogenic cells cultured densely to differentiate and, conversely, the resistance to differentiation of cells at
low density has been called the 'Community Effect'; understanding this phenomenon represents a basic
question in muscle biology. Based on our initial observation that EphA7, a juxtacrine signaling molecule, is
expressed on myocytes during embryonic and fetal myogenesis and on nascent myofibers during muscle
regeneration in vivo we examined the muscle phenotype of EphA7-/- mice. We found that their hindlimb
muscles possess fewer myofibers at birth, and those myofibers are reduced in size and have fewer
myonuclei and reduced overall numbers of precursor cells throughout postnatal life. Adult EphA7-/- mice
have reduced numbers of satellite cells and exhibit delayed and protracted muscle regeneration, and
satellite cell-derived myogenic cells from EphA7-/- mice are delayed in their expression of differentiation
markers in vitro. Exposure to exogenous EphA7 extracellular domain will rescue the null phenotype, and will
also accelerate commitment to differentiation in WT cells, which led us to propose a model in which EphA7
expression on differentiated myocytes promotes commitment of adjacent myoblasts to terminal
differentiation via reverse signaling. The experiments we propose in Aims 1 and 2 will address the role of
EphA7 in myogenic commitment in both the myocyte ("How does commitment to differentiation lead to
expression of EphA7?") and the myoblast ("How does receiving an EphA7 signal lead to commitment to
differentiation?"). Once they have differentiated, myocytes must fuse with each other or with a growing
myotube in order to generate a functional muscle cell (the contractile myocyte fiber), thus this also
represents a critical process in both development and regeneration. However, the molecular requirements
for fusion in mammalian muscle cells have been elusive. Our data suggest EphA7 also promotes myogenic
fusion, possibly via different molecular mechanisms/interactions from its role in promoting myogenic
differentiation. The experiments we propose in Aim 3 will test the ability of EphA7 to promote fusion in
myogenic and nonmyogenic cells, determine whether it associates with the cell-surface fusogen myomaker,
and identify other protein-protein interactions it is participating in at the interface of myocytes and growing
myotubes in cis (on the same cell membrane) or in trans (on opposing cell membranes). Collectively, these
studies will address the molecular mechanisms regulating two fundamental cellular processes during
myogenic differentiation; they also have the potential to provide insight into potential innovat...

## Key facts

- **NIH application ID:** 10219157
- **Project number:** 5R01AR078045-02
- **Recipient organization:** UNIVERSITY OF MISSOURI-COLUMBIA
- **Principal Investigator:** Dawn D Cornelison
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $316,812
- **Award type:** 5
- **Project period:** 2020-07-17 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10219157

## Citation

> US National Institutes of Health, RePORTER application 10219157, EphA7 promotes contact-dependent myogenesis (5R01AR078045-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10219157. Licensed CC0.

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