# Investigating RhoA GTPase regulation in sculpting tissues

> **NIH NIH R01** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2021 · $314,506

## Abstract

Project Summary/Abstract
During development, the actomyosin cytoskeleton serves as a machine to generate
contractile force. Sculpting tissues requires this force-generating machine to be
precisely regulated in both space and time. The small GTPase RhoA coordinates both
myosin motor activation and actin filament assembly, to promote contractility. RhoA is
pivotal in regulating actomyosin contractility in numerous developmental contexts,
including epithelium folding. One common feature of actomyosin contractility, during
both Drosophila gastrulation and Xenopus neural tube closure, is that actomyosin
exhibits oscillatory dynamics. Actomyosin dynamics are critical for epithelial folding in
both Drosophila gastrulation and the Xenopus neural tube. In Drosophila, these
dynamics require negative regulation of RhoA via a GTPase Activating Protein (GAP).
Aim 1 of this proposal aims to understand how this Drosophila GAP is regulated to
promote actomyosin dynamics and tissue folding. In addition, we have discovered a
novel oscillatory behavior for an upstream guanine nucleotide exchange factor (GEF),
which activates RhoA. Aim 2 of this proposal seeks to understand the mechanism that
regulates this Drosophila GEF and, thus, paces actomyosin contractility. Overall, these
two aims will determine how the partnership of a specific GEF and GAP precisely
regulate RhoA signaling to promote tissue folding. Because Rho-family GTPases are
critical regulators of tissue structure and there are many GEFs and GAPs for Rho-family
GTPases, Aim 3 will determine the regulatory logic that influences GTPase activity for
other morphogenetic processes in Drosophila. First, we will examine a change in tissue
integrity, epithelial-to-mesenchymal transition (EMT). We will determine mechanisms
by which GTPase regulation promotes this transition and, thus, loss of epithelial
integrity. Finally, we will perform a screen to identify additional combinations of GEFs
and GAPs that regulate other tissue shape changes. Our overall goal is to better define
how Rho-family GEFs, GAPs, and their cognate GTPases function to precisely control
tissue shape and integrity.

## Key facts

- **NIH application ID:** 10070108
- **Project number:** 5R01GM125646-04
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Adam Christopher Martin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $314,506
- **Award type:** 5
- **Project period:** 2018-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10070108

## Citation

> US National Institutes of Health, RePORTER application 10070108, Investigating RhoA GTPase regulation in sculpting tissues (5R01GM125646-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10070108. Licensed CC0.

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