# Planar cell polarity control of axon guidance

> **NIH NIH R37** · FRED HUTCHINSON CANCER CENTER · 2024 · $597,738

## Abstract

PROJECT SUMMARY
Midline crossing by dorsal commissural axons is a prominent feature of vertebrate and invertebrate nervous
systems, necessary for the left-right coordination of sensory and motor systems, locomotion, and posture. In the
vertebrate spinal cord, dorsal commissural axons extend towards and cross the midline floorplate, and then turn
longitudinally to ascend towards the brain. While the growth cone’s voyage to and across the floorplate has been
intensively studied, its final decision—whether to ascend or descend after emerging from the midline—is less
well understood. Genetic studies clearly implicate the Planar Cell Polarity (PCP) pathway in this decision, but
our understanding of how PCP signaling guides the growth cone is incomplete. The PCP pathway is a cell-cell
contact-mediated signaling pathway that transmits polarity information between cells to orient them for directed
migration. Yet our mechanistic understanding of the role of PCP signaling in commissural axon guidance is
largely informed by studies of isolated growth cones in vitro. Thus, A major gap in our understanding of
commissural axon guidance is the role that cell contact-mediated cues play in longitudinal guidance. Using the
transparent zebrafish embryo to visualize the axons and growth cones of single identified pioneer commissural
interneurons in PCP mutants, we have found that core components of the PCP signaling pathway are required
equally within the commissural neuron and in its environment for correct axon targeting. PCP proteins localize
to the growth cone and to the cells on its trajectory. We hypothesize that the growth cone uses PCP signaling to
polarize its growth in response to planar-polarized cues in its immediate neuroepithelial environment. In Aim 1
we will test this hypothesis by locating, in space and time, the requirement for PCP core components in the
growth cone environment, and by quantitative live imaging of growth cone membrane and actin dynamics as it
is making its anterior targeting decision. In Aim 2 we will expand our scope to discover the commissural axon
guidance role of proteins that have been implicated in PCP signaling elsewhere through a targeted G0 CRISPR
screen. Finally, in Aim 3 we will expand our scope once again to test the hypothesis that PCP signaling functions
broadly in longitudinal axon guidance in the spinal cord. The successful outcome of this work will be a deep
mechanistic understanding of how the dorsal commissural neuron growth cone is polarized for anterior growth
in vivo by the Planar Cell Polarity pathway, to enable it to build sensory circuits controlling locomotion and
posture.

## Key facts

- **NIH application ID:** 10892878
- **Project number:** 5R37NS131117-02
- **Recipient organization:** FRED HUTCHINSON CANCER CENTER
- **Principal Investigator:** Cecilia B Moens
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $597,738
- **Award type:** 5
- **Project period:** 2023-08-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10892878

## Citation

> US National Institutes of Health, RePORTER application 10892878, Planar cell polarity control of axon guidance (5R37NS131117-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10892878. Licensed CC0.

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