# Notch Signaling in non-myogenic mesenchymal cells regulates muscle development

> **NIH NIH F31** · DUKE UNIVERSITY · 2021 · $38,425

## Abstract

ABSTRACT
The majority of research on muscle development focuses on the specific regulation and direct contribution of myogenic
progenitors and myoblasts to muscle formation. Recently, non-myogenic mesenchymal cells (NMMCs) located within
developing muscle tissues have been identified as critical regulators of normal myogenesis. These studies show that
muscle development or regeneration cannot occur in the absence of specific non-myogenic mesenchymal “niche”
cells. In order to genetically examine regulatory mechanisms that may be critical for NMMC function and normal muscle
development, our lab has demonstrated the utility of the Prx1Cre in accessing the broad class of NMMCs within skeletal
muscle. Flow cytometry and scRNA sequencing of the Prx1 lineage not only confirmed that multiple populations of
NMMCs exist within the skeletal muscle, but also that these populations are responsive to NOTCH signaling. Further,
preliminary results indicate that a conditional loss of NOTCH within NMMCs (NOTCH LOF, Prx1Cre; RBPJkf/f) impairs
normal muscle development and function. Given this, we hypothesize that NOTCH mediated regulation of NMMCs
is critical for normal skeletal muscle development and function. In testing this hypothesis, we will utilize a
combination of in vivo and in vitro methods in order to: (Aim 1) determine the role of NOTCH signaling in non-myogenic
mesenchymal progenitors during muscle development in vivo and (Aim 2) evaluate the cellular mechanisms by which
NMMC-mediated NOTCH signaling regulates skeletal muscle in vitro. Our findings will further our fundamental
understanding of muscle development, specifically, our understanding of niche regulation and dynamics during muscle
formation and function. Additionally, these findings may provide key insights into the role(s) of NMMC-derived NOTCH
signaling in diseases affecting muscle development, and may also aid in future studies of muscle regeneration where
disruption of the NMMC niche prevents proper myogenesis.

## Key facts

- **NIH application ID:** 10150458
- **Project number:** 5F31AR076180-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Abigail leinroth
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $38,425
- **Award type:** 5
- **Project period:** 2020-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10150458

## Citation

> US National Institutes of Health, RePORTER application 10150458, Notch Signaling in non-myogenic mesenchymal cells regulates muscle development (5F31AR076180-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10150458. Licensed CC0.

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