# Control of epithelial morphology and bioenergetics by Toll receptors during dynamic tissue remodeling

> **NIH NIH P20** · UNIVERSITY OF ARKANSAS AT FAYETTEVILLE · 2021 · $218,957

## Abstract

Project Summary – Project Leader Adam Paré
Epithelial cells undergo significant changes in shape and relative position during development to build proper
tissue architecture. Errors in epithelial remodeling directly contribute to some of the most common types of
congenital abnormalities––neural tube defects––which affect approximately 1 in 2000 births. However, the
upstream signals that control epithelial morphology remain poorly understood. A paradigm for studying epithelial
remodeling is cell intercalation in the Drosophila neurectoderm, and it was shown that three members of the
highly conserved Toll receptor family are expressed in overlapping striped patterns to organize rapid cell
rearrangements in this tissue. Toll receptors are widely expressed throughout human epithelia, and they have
been extensively studied in the context of innate immune signaling. However, the control of cell morphology by
Toll receptors has received very little attention. The focus of this proposal is to understand how non-uniform Toll
receptor expression affects cortical tension, cell-cell adhesion, and mitochondrial dynamics to control cell shape
and behavior during epithelial remodeling. We will use newly developed CRISPR/Cas9-derived genetic
backgrounds and antibodies to characterize how Toll receptors control cell polarity to trigger intercalation; we
will apply non-destructive techniques to characterize the bioenergetics of epithelial reorganization in intact living
embryos; and we will investigate unaddressed links between Toll receptor, Rho, and G protein-coupled receptor
signaling. Our first hypothesis is that neighboring cells sense differences in the expression of individual Toll
receptor types to increase cortical tension and decrease cell-cell adhesion. We have developed a genetic system
for expressing individual receptors in a single stripe that we will use to systematically characterize and compare
the effects of each Toll receptor type on cell morphology and to identify the protein domains necessary for
modulating cell shape. Our second hypothesis is that rapid cellular rearrangements during neurectoderm
elongation require specific changes in mitochondrial architecture to fuel cytoskeletal and junctional
reorganization. To test this, we will use the Agilent Seahorse flux analyzer to measure oxygen consumption rates
and multiphoton microscopy to visualize cellular redox state in live embryos during epithelial remodeling, and
then use gain- and loss-of-function techniques to determine what role mitochondrial fusion and fission play in
epithelial reorganization. Our third hypothesis is that Toll receptor and GPCR signaling converge to activate Rho
Kinase to trigger cell intercalation specifically in the neurectoderm. We will use gain- and loss-of-functional
analyses to determine how these two signaling pathways intersect to control cortical tension, cell-cell adhesion,
mitochondrial dynamics during epithelial remodeling. Successful completion of these e...

## Key facts

- **NIH application ID:** 10090750
- **Project number:** 1P20GM139768-01
- **Recipient organization:** UNIVERSITY OF ARKANSAS AT FAYETTEVILLE
- **Principal Investigator:** Adam Christopher Pare
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $218,957
- **Award type:** 1
- **Project period:** 2021-04-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10090750

## Citation

> US National Institutes of Health, RePORTER application 10090750, Control of epithelial morphology and bioenergetics by Toll receptors during dynamic tissue remodeling (1P20GM139768-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10090750. Licensed CC0.

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