# Mechanisms that Coordinate Cellular Movements for Epithelial Migration

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 2021 · $359,772

## Abstract

PROJECT SUMMARY / ABSTRACT
Collective migration of epithelial cells is essential for embryonic development, wound healing and the spread of
some cancers. For an epithelium to migrate, the cytoskeletal machinery that powers each cell’s motility must
become globally aligned across the tissue. It is likely that diverse cell-cell and cell-matrix signals are integrated
to achieve this goal. However, few of these signals have been identified and even fewer are understood at a
mechanistic level. The goal of this research is to define the signals that orient the migration machinery for
epithelial motility, and to use this knowledge to generate new ideas for wound healing and cancer therapies.
 To this end, we are using genetic, cell biological, and high resolution live imaging approaches to study
a dramatic collective migration that occurs in the Drosophila follicular epithelium. The cytoskeletal machinery
that powers this tissue’s movement shows a particularly high degree of global alignment, a pattern that is best
seen through the alignment of contractile actin stress fibers across the tissue. Because stress fibers generate
traction forces for individual cell motility though their interaction with integrin-based adhesions, their global
alignment is essential for efficient collective movement. Aligned stress fibers are also seen in mammals, with
notable examples being the collective migrations of endothelial cells and the epithelial cells of the cornea and
lens. However, little is known about how this tissue-level actin network is generated.
 The Specific Aims in this proposal will explore how three distinct signals impact different aspects of the
stress fiber alignment program: initiation, reinforcement/stabilization, and local disassembly. Aim 1 will test the
hypothesis that cell protrusive activity, as induced by signaling from the Fat2 cadherin, can initiate global stress
fiber alignment as migration begins. Aim 2 will investigate whether a novel polarized feature within the
basement membrane (BM) ECM that we have termed BM ridges reinforces and/or stabilizes the global stress
fiber pattern. Finally, Aim 3 explores whether a newly identified semaphorin signal helps to control the local
disassembly of stress fibers that is required for forward movement to occur. Our discovery of the semaphorin’s
role in epithelial motility, as well as the key entry points for Aims 1 and 2, all came from a small-scale genetic
screen. Thus, to continue to gain novel insights into the signaling mechanisms that promote epithelial motility,
work proposed in Aim 3 will also extend our successful screening strategy to other regions of the genome.
 The signals we propose to study have been implicated in epithelial migrations in mammals, but how
they promote collective motility is unknown. Thus, by defining the cell-cell and cell-matrix signals that generate
and maintain the tissue-level stress fiber pattern in the follicular epithelium, we will provide a general paradigm
for...

## Key facts

- **NIH application ID:** 10067553
- **Project number:** 5R01GM126047-04
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Sally Horne-Badovinac
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $359,772
- **Award type:** 5
- **Project period:** 2018-02-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10067553

## Citation

> US National Institutes of Health, RePORTER application 10067553, Mechanisms that Coordinate Cellular Movements for Epithelial Migration (5R01GM126047-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10067553. Licensed CC0.

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