# Genetic Regulation of Muscle Fiber Diversity

> **NIH NIH R01** · SAN DIEGO STATE UNIVERSITY · 2020 · $13,548

## Abstract

Genetic regulation of muscle fiber diversity
The long-term goal of this project is to create a developmental regulatory framework to describe how
diverse skeletal muscle fiber types are specified. Mammalian muscles contain distinct fiber types with
unique physiologies, however the manner in which fiber-type development occurs has yet to be fully
elucidated. We use the Drosophila system to understand mechanisms of muscle fiber differentiation,
by analyzing the development of two distinct muscles in the adult thorax: the flight muscles and jump
muscles, which are members of two distinct fiber types. In the current period of support, we
discovered that the transcription factors Extradenticle (Exd) and Homothorax (Hth) activate a
regulatory cascade involving another transcription factor, Spalt-major (Salm), and the CELF-related
splicing factor Arrest (Aret). This network promotes specification of the flight muscles through direct
activation of at least one flight muscle structural gene, and through direct regulation of flight muscle-
specific alternative splicing events. Each factor can also promote flight muscle fate in the jump
muscle, indicating that they are critical to fiber-specific gene regulation. Importantly, Exd, Hth and
Aret have vertebrate homologs known to function in promoting fast fiber fate. In the next period of
support, we will build upon this framework to generate a complete view of how fiber-specific identity is
controlled, and expand our analysis to define how jump muscle differentiation is controlled. We will
also investigate how the transcriptional pathways for formation of individual fiber types interact with
one another to maintain their own identity, and to suppress formation of the other fiber type. Given
that Exd, Hth and Aret each have vertebrate orthologs that contribute to fiber-specific gene regulation,
our studies stand to provide critical new insight into mechanisms of muscle formation in vertebrates,
and will generate a framework for understanding the basis of fiber-specific gene regulation in
mammalian development and disease.

## Key facts

- **NIH application ID:** 9937418
- **Project number:** 3R01GM061738-18S1
- **Recipient organization:** SAN DIEGO STATE UNIVERSITY
- **Principal Investigator:** Richard Matthew Cripps
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $13,548
- **Award type:** 3
- **Project period:** 2001-05-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9937418

## Citation

> US National Institutes of Health, RePORTER application 9937418, Genetic Regulation of Muscle Fiber Diversity (3R01GM061738-18S1). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/9937418. Licensed CC0.

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