# The emergence of collective cell behaviors from intercellular interactions

> **NIH NIH R01** · PRINCETON UNIVERSITY · 2024 · $411,930

## Abstract

Project Summary
Embryos and organs are shaped by complex collective cell movements involving the coordinated action
of thousands of cells over space and time. Impairments in collective cell motion underlie many
structural birth defects, the most common of which is the failure to close the neural tube leading to
spina bifida, exencephaly, or most severely craniorachischisis. One of the key challenges in
developmental biology and tissue engineering is understanding the molecular mechanisms by which
cells coordinate their behaviors across thousands of cells to generate large-scale changes in tissue
forms through local changes in subcellular organization. The planar cell polarity pathway (PCP) has
emerged as a key regulator that organizes individual cell behaviors into large-scale collective cell
movements, and is essential for the proper formation of most organ systems in vertebrates. Given the
diversity of structures whose morphogenesis relies on PCP, a central challenge is to define a common,
unifying set of molecular principals through which PCP acts. Specifically, the molecular links between
PCP components and their downstream effectors are poorly defined. Moreover, we do not understand
how polarity within individual cells is coordinated into collective, tissue-scale behaviors. Defining these
molecular links in detail and connecting them to higher order patterns of collective cell behavior is thus
crucial to our basic understanding of tissue morphogenesis.
 The murine epidermis displays striking spatial and directional patterns, and is an ideal model
system to approach these questions. Using newly developed live imaging capabilities, we recently
discovered two novel collective cell movements during formation of epithelial placodes in the
mammalian skin. These movements bear resemblance to the behaviors that underlie embryonic germ
layer formation and gastrulation, suggesting that deeply conserved mechanisms underlie the
morphogenesis of very diverse structures. We propose to use the power of the murine epidermis to
gain a molecular understanding of these Wnt and PCP-dependent collective cell movements. Specific
Aim 1 will define the mechanisms of PCP-mediated force generation and symmetry breaking that drive
collective cell motion. Specific Aim 2 will elucidate how patterns of differential cell adhesion promote
epithelial motility and prevent cell mixing to compartmentalize collective epithelial movements. Specific
Aim 3 will decipher the mechanisms driving epithelial rearrangements during periodic pattern formation.
Our findings will define how local, intercellular interactions generate the large-scale collective
movements that occur during organogenesis and reveal how structural birth defects arise when these
processes go awry.

## Key facts

- **NIH application ID:** 10836479
- **Project number:** 5R01HD105009-03
- **Recipient organization:** PRINCETON UNIVERSITY
- **Principal Investigator:** Danelle N Devenport
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $411,930
- **Award type:** 5
- **Project period:** 2022-06-24 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10836479

## Citation

> US National Institutes of Health, RePORTER application 10836479, The emergence of collective cell behaviors from intercellular interactions (5R01HD105009-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10836479. Licensed CC0.

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