# Protrusive behavior during collective cell migration

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2022 · $308,000

## Abstract

Cell migration is one of the fundamental processes shaping the developing embryo. Collective cell migration is
a specialized form of coordinated cellular migration where cells maintain cell-cell contacts, group polarization,
and coordinated behavior. Collective cell migration is essential for numerous processes during development,
including neural tube closure, blood vessel branching, and neural crest cell migration. Consequently, disruption
of this process during development can lead to severe birth defects. There is also a growing body of evidence
that epithelial tumor cells move as cohesive groups during tissue invasion, in a process termed collective cell
invasion, which is analogous to collective cell migration during embryogenesis. Thus, a mechanistic
understanding of collective cell migration should provide important new insights into tissue morphogenesis
during embryogenesis and abnormal cell migration in diseases. However, the molecular mechanisms that
regulate collective cell migration remain poorly defined. As cells migrate, they must extend protrusions to
interact with the extracellular environment, sense chemotactic cues, and act as points of attachments and
signaling centers to coordinate the migratory behavior. The regulators of protrusive behavior have been widely
studied in cells that migrate individually; however, how protrusive behavior is controlled throughout collectives
is not well understood. To tackle this problem, we are using unique advantages of the zebrafish model system,
including amenity to live imaging and advanced genetic approaches. Using mosaic labeling of filamentous
actin, we discovered an abundance of brush-like, actin-based protrusions in multiple cells across the migrating
collective. Live imaging revealed that these previously undescribed structures are highly dynamic, oriented
towards the direction of migration, and prevalent in the leading part of the collective. We further demonstrated
that these protrusions are Arp2/3 dependent and are required for collective cell migration. We have previously
shown that the canonical Wnt signaling is necessary for cell movement during collective cell migration. We
have also found that a high number of Wnt target genes are known regulators of actin dynamics; these genes
are expressed in distinct regions of the collective and their expression pattern is perturbed under Wnt-deficient
conditions. We therefore hypothesize that protrusive behavior during collective cell migration is coordinated by
a differential activity of Wnt target genes that regulate actin dynamics. To test this hypothesis, we will 1)
define the type of protrusions and molecular machinery that regulates their activity; 2) determine the role of
major signaling pathways, including Wnt and Fgf, in regulating this behavior; and 3) identify novel regulators of
protrusive behavior during collective cell migration. Better understanding of collective cell migration during
organ development will help to elucidate...

## Key facts

- **NIH application ID:** 10376331
- **Project number:** 5R01GM130868-03
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Alex Nechiporuk
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $308,000
- **Award type:** 5
- **Project period:** 2020-06-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10376331

## Citation

> US National Institutes of Health, RePORTER application 10376331, Protrusive behavior during collective cell migration (5R01GM130868-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10376331. Licensed CC0.

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