# Maintenance of Adhesion and Barrier Function during Epithelial Cell Shape Changes

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $341,663

## Abstract

PROJECT SUMMARY / ABSTRACT
Cell-cell junctions adhere epithelial cells to one another, transmit forces from cell to cell, and generate
biological barriers that selectively regulate what can pass between cells in an epithelial tissue. Fundamental
questions about how epithelial cell-cell junctions dynamically remodel in response to physiological forces that
that challenge cell adhesion and barrier function remain unanswered. In addition to being absolutely essential
for development and maintenance of organ homeostasis, disruption of adhesion and barrier function
contributes to diseases including cancer cell metastasis and Inflammatory Bowel Disease. Therefore, it is
critical to determine the mechanisms that control cell-cell junction remodeling as epithelial cells change shape.
This proposal builds on recent discoveries from the lab showing that Rho flares locally reinforce tight junctions
following leaks in barrier function, and that adherens junctions are reinforced by recruitment of Vinculin to the
cleavage furrow of dividing epithelial cells. The overall objective of this application is to identify mechanisms
that promote maintenance of adhesion and barrier function at sites of epithelial cell division and junction
elongation. Our central hypothesis is that locally applied mechanical forces challenge adherens junctions and
tight junctions and elicit actomyosin-mediated reinforcement required for maintenance of adhesion and barrier
function at these sites. The central hypothesis will be tested by pursuing three specific aims: 1) Identify how
mechanically-induced tight junction leaks trigger Rho flares; 2) Determine how Rho flare-mediated junction
contractility repairs tight junctions; 3) Define mechanisms that mediate tension transmission and barrier
maintenance at sites of locally increased tension. The proposed research is innovative because it applies
powerful experimental tools including: a developing vertebrate model system (Xenopus laevis embryos), a live
imaging barrier assay recently developed in the lab, proven approaches to locally or globally manipulate
tension in the intact epithelium, probes for live imaging of active Rho dynamics as well as a host of cytoskeletal
proteins, junction proteins, Rho regulators, and cytoplasmic calcium, and specialized analysis tools to
quantitatively analyze live imaging data. The proposed research is significant because it will advance our
knowledge about a fundamentally important problem in epithelial cell biology: how epithelial cells undergo
dramatic cell shape changes like cytokinesis yet maintain tissue integrity and barrier function.

## Key facts

- **NIH application ID:** 9970722
- **Project number:** 2R01GM112794-06
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Ann Louise Miller
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $341,663
- **Award type:** 2
- **Project period:** 2015-08-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9970722

## Citation

> US National Institutes of Health, RePORTER application 9970722, Maintenance of Adhesion and Barrier Function during Epithelial Cell Shape Changes (2R01GM112794-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9970722. Licensed CC0.

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