# Multiscale coordination of planar cell polarity

> **NIH NIH R01** · PRINCETON UNIVERSITY · 2020 · $421,777

## Abstract

PROJECT SUMMARY
Cells have a remarkable capacity to self-assemble into organ-like structures in vitro. However,
current in vitro-derived organs lack proper size and higher-order patterning, features that require
organism-level information not present in a dish. Notably, the collective polarization and
unidirectional alignment of cells across a tissue, a phenomenon known as planar cell polarity
(PCP), is lacking in vitro organs, yet is essential for proper organ formation and function. Thus, to
fulfill the promise of tissue engineering to generate functional organs in vitro we must understand
how cells establish long-range collective polarization.
 We have established the murine skin as a model system to investigate the multiscale
coordination of PCP in an expansive and regenerative tissue. By developing methods to perform
ex vivo culturing, long-term live imaging, biophysical perturbations, and organotypic reconstitution
of the epidermis, we have made key new discoveries about PCP establishment at the tissue,
cellular and molecular scales. We discovered that uniaxial tissue deformation acts as a symmetry
breaking cue that defines the major axis of PCP alignment in the epidermis. We further showed
that that primary keratinocytes grown in the absence of global cues establish spontaneous, locally
aligned domains of planar polarity de novo. Through super-resolution imaging and mapping the
adhesive interactions of PCP components, we identified a role for cadherin-mediated cis-
interactions in the clustering and sorting of asymmetric PCP complexes.
 The broad goal of this work is to build on these previous discoveries and technological
developments to decipher how PCP is organized across different biological length scales. Using
the mammalian skin epidermis as a model system, Specific Aim 1 will determine how long-range
mechanical cues bias and align planar cell polarity across the epidermis. Specific Aim 2 will
investigate the mechanisms by which cells skin cells spontaneously generate PCP through self-
organization. Specific Aim 3 will decipher the nanoscale architecture and biochemical
interactions of PCP complexes. Using technical innovations recently developed in my laboratory
to perform live and super-resolution imaging of endogenously-tagged PCP proteins in both native
and organotypic tissues, this work will provide fundamental new insights into the multiscale
coordination of PCP.

## Key facts

- **NIH application ID:** 9972046
- **Project number:** 2R01AR066070-06
- **Recipient organization:** PRINCETON UNIVERSITY
- **Principal Investigator:** Danelle N Devenport
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $421,777
- **Award type:** 2
- **Project period:** 2015-04-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9972046

## Citation

> US National Institutes of Health, RePORTER application 9972046, Multiscale coordination of planar cell polarity (2R01AR066070-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9972046. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*