# Genetic Regulation of Muscle Fiber Diversity

> **NIH NIH R01** · SAN DIEGO STATE UNIVERSITY · 2020 · $406,187

## Abstract

Project Summary/Abstract:
The overall goal of this project is to define the mechanisms that are used to generate diverse muscle fiber
types. In animals, different muscle fiber types arise to fine-tune the functions of individuals muscles, to enable
those muscles to carry out their distinct roles in the animal. However, there is still much to learn of the cellular
and molecular mechanisms that direct groups of myoblasts towards one fiber fate versus others. We have
demonstrated that the flight muscles of the adult Drosophila thorax are specified and differentiate using
mechanisms that are conserved with vertebrate fast fiber specification. Moreover, we have identified a number
of transcriptional regulators that are required for formation of the flight muscles or of the physiologically-distinct
jump muscles. In this renewal, we will build upon our studies to define conserved signaling and transcriptional
pathways that give rise to different adult muscle fiber types. In the first aim, we will determine how ectodermal
signals such as Wingless specify flight muscle specification via Vestigial and the flight muscle identity factor
Spalt-major. In the second aim, we will define the roles of orthologs of mammalian Mohawk and Sox6 in
regulating muscle fiber identity. In the third aim, we will focus upon how Vestigial and its cofactor Scalloped
regulate jump muscle differentiation. Overall, our studies will provide significant new insight into how different
muscle fiber types are generated during development in Drosophila. Importantly, our published and preliminary
data provide significant evidence that conserved mechanisms regulate muscle fiber fate choices, indicating
that our findings can be used as a valuable framework for understanding vertebrate muscle specification.
Moreover, since muscle diseases and diabetes often affect the prevalence of one muscle fiber type over
another, understanding the normal mechanisms of muscle fiber specification and maintenance can provide
insight into the diseased state and how those conditions might be ameliorated.

## Key facts

- **NIH application ID:** 9894813
- **Project number:** 5R01GM061738-19
- **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:** $406,187
- **Award type:** 5
- **Project period:** 2001-05-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9894813

## Citation

> US National Institutes of Health, RePORTER application 9894813, Genetic Regulation of Muscle Fiber Diversity (5R01GM061738-19). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9894813. Licensed CC0.

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