# Molecular genetic analysis of MEF2 function in Drosophila

> **NIH NIH R01** · SAN DIEGO STATE UNIVERSITY · 2024 · $431,685

## Abstract

Project Summary/Abstract.
Members of the Myocyte enhancer factor-2 (MEF2) family of transcription factors play prominent roles in the
differentiation of the musculature, and changes in MEF2 function are strongly associated with human disease
mechanisms. Central to understanding the mechanistic basis of MEF2-dependent disease is an understanding
of the normal function of this important factor. Research over many years has uncovered numerous cofactors
that impact MEF2 function, however we still lack a full understanding of the global regulation of MEF2 function
during muscle development, and of how that process goes awry in the diseased state.
 Our research uses the Drosophila model system, whose genome contains a single Mef2 gene, thus
obviating complications arising from genetic redundancy. In addition, Drosophila contains muscle types similar
to those in humans, and which are specified using mechanisms that are conserved across the animal kingdom.
Therefore, the developmental and disease mechanisms that we uncover in flies will be directly relevant to
understanding human health. Drosophila also is highly amenable to genetic manipulation and genetic screens.
 During the current period of support, we have used a range of approaches to identify and characterize
interactions and modifications of MEF2 that regulate its function, and we have uncovered new global
mechanisms that impact MEF2 in the contexts of both development and disease. In this proposal, we will test
the overarching hypothesis that MEF2 function is regulated by dueling positively and negatively acting
processes, and we will carry out both hypothesis-driven and genetic screening approaches to understand this
regulation at the molecular level. In Aim 1 we will determine mechanistically how MEF2 function in myoblasts is
restrained by epigenetic mechanisms and test the hypothesis that the NuRD complex functions in this process.
In Aim 2 we will define the in vivo functional significance of MEF2 interaction with P38 MAPK and define how
this post-translational modification of MEF2 affects interactions with the processes characterized in Aim 1.
These approaches will provide novel and impactful new insight into the mechanisms of MEF2 function, and
how mutations affecting MEF2 can result in human disease.

## Key facts

- **NIH application ID:** 10882809
- **Project number:** 2R01GM124498-06A1
- **Recipient organization:** SAN DIEGO STATE UNIVERSITY
- **Principal Investigator:** Richard Matthew Cripps
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $431,685
- **Award type:** 2
- **Project period:** 2017-09-01 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10882809

## Citation

> US National Institutes of Health, RePORTER application 10882809, Molecular genetic analysis of MEF2 function in Drosophila (2R01GM124498-06A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10882809. Licensed CC0.

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