# Planar cell polarity mechanisms and systems architecture

> **NIH NIH R35** · STANFORD UNIVERSITY · 2023 · $979,390

## Abstract

Summary/Abstract
Planar cell polarity (PCP) signaling controls the polarization of cells within the plane of an epithelium,
orienting asymmetric cellular structures, cell divisions and cell migration and is well conserved from
Drosophila to vertebrates. Most of our mechanistic understanding of PCP signaling has and will
likely continue to derive from work using Drosophila as a model system. In flies, PCP signaling
controls the orientation of hairs on the adult cuticle, chirality and orientation of ommatidia in the eye,
orientation of cell divisions, and related processes in other tissues.
While much of our focus is on mechanistic studies in flies, numerous medically important
developmental defects and physiological processes in vertebrates are also under control of PCP
signaling, motivating considerable interest in studying PCP both in Drosophila and in vertebrate
model systems. In vertebrates, defects in the core PCP mechanism result in a range of
developmental anomalies and diseases including open neural tube defects, conotruncal heart
defects, deafness and situs inversus and heterotaxy, and has been (incorrectly) implicated in
polycystic kidney diseases. PCP is also believed to underlie the directed migration of malignant cells
during invasion and metastasis and during wound healing. PCP polarizes skin and hair and the
ependyma. The PCP component Prickle, though perhaps not involving the PCP pathway, is mutated
in an epilepsy-ataxia syndrome. Mutations in `global' PCP components have recently been
associated with a human disorder of neuronal migration and proliferation. These phenotypes can be
studied in vertebrate models of PCP gene mutants, and provide excellent opportunities to
understand vertebrate PCP signaling and its morphogenetic manifestations. Cellular behaviors
controlled by PCP in vertebrates vary, and the expanded numbers of paralogs for the PCP genes in
mouse compared to flies suggests the possibility of functional diversification. Hence there is a strong
need to understand how PCP signaling is adapted in these various contexts.
This proposal aims to dissect the molecular and cell biological mechanisms of PCP signaling using
Drosophila as a model system and to extend our understanding to selected vertebrate PCP
signaling events. The proposed work will both enhance our knowledge of fundamental mechanisms
as well as lay the groundwork for potential therapeutic interventions for PCP related pathologies.

## Key facts

- **NIH application ID:** 10692917
- **Project number:** 5R35GM131914-05
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Jeffrey D. Axelrod
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $979,390
- **Award type:** 5
- **Project period:** 2019-09-16 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10692917

## Citation

> US National Institutes of Health, RePORTER application 10692917, Planar cell polarity mechanisms and systems architecture (5R35GM131914-05). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10692917. Licensed CC0.

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