# Trio/CARMIL Regulation of Epithelial Cell Rearrangement

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $300,912

## Abstract

Project Summary
The directed rearrangement of epithelial cells is crucial during human development, including
the events of gastrulation and neurulation. How basolateral protrusive activity contributes to this
process is poorly understood. Dorsal intercalation in the epidermis of the C. elegans embryo is
an outstanding model system for examining basolateral events during epithelial cell
rearrangement at the level of single cells. We have shown that dorsal intercalation relies on a
phylogenetically conserved Rac/RhoG cassette activated by the Rho family guanine nucleotide
exchange factor (GEF), UNC-73/Trio, and is negatively regulated by the highly conserved actin
capping protein regulator, CRML-1/CARMIL (capping protein-, Arp2/3- and myosin I-linker
protein).
This new proposal will investigate how this conserved Rac/RhoG cassette regulates directed
cell rearrangement by performing experiments in four areas:
(1) We will use embryological and structure-function approaches to determine how CRML-
1/CARMIL localizes to the rear of intercalating cells;
(2) We will use biochemical and in vivo rescue experiments to determine whether CRML-1
negatively regulates the Trio/Rac/RhoG pathway via direct binding or indirectly through its
effects on capping protein recruitment;
(3) We will determine whether a Slit/Robo/srGAP cassette regulates Rac via localized repulsion
or as a “cell contact buffer”; and
(4) We will determine how additional components regulate the Trio/Rac/RhoG pathway using
candidate screens and forward genetic approaches.
As a result of these studies, we will elucidate a novel pathway regulating cell intercalation via
basolateral protrusive activity, a widespread process with implications for understanding major
birth defects and normal human embryogenesis.

## Key facts

- **NIH application ID:** 9903409
- **Project number:** 5R01GM127687-03
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Jeffrey D Hardin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $300,912
- **Award type:** 5
- **Project period:** 2018-05-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9903409

## Citation

> US National Institutes of Health, RePORTER application 9903409, Trio/CARMIL Regulation of Epithelial Cell Rearrangement (5R01GM127687-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9903409. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*