# NADPH oxidase regulates growth cone guidance

> **NIH NIH R01** · PURDUE UNIVERSITY · 2020 · $335,649

## Abstract

Reactive oxygen species (ROS) can act as signaling molecules mediating physiological functions in immunity,
cell proliferation, differentiation, and migration. Whether ROS have a major signaling function as second
messengers in axonal growth and guidance is currently unclear. The neuronal growth cone is a highly motile
structure at the tip of neuronal processes, guiding them to appropriate target cells during development and
regeneration of the nervous system. The growth cone integrates molecular information from the environment
and transduces it via multiple signaling cascades to affect underlying cytoskeletal dynamics. Whereas most
major second messenger systems have been implicated in regulating directional growth cone movement, such
a role has not been established for ROS. The present study has two major objectives focusing on ROS produced
by nicotinamide adenine dinucleotide phosphate-(NADPH) oxidase (Nox): (1) to determine the cellular and
molecular mechanism by which ROS control neurite growth; and (2) to determine whether ROS act as second
messengers downstream of specific guidance cues to control axonal growth and guidance. The four central
hypotheses state that (1) a physiological level of ROS is optimal and required for adhesion-mediated neurite
growth; (2) Src tyrosine kinase is a key target of ROS signaling in neuronal growth cones; (3) neuronal Nox2-derived ROS regulate axonal pathfinding; and (4) specific axon guidance cues such as slit2 control axonal
pathfinding via Nox2-derived ROS both in vitro and in vivo. This project will take advantage of two excellent
model systems to test these hypotheses: large Aplysia growth cones for quantitative live cell imaging of growth
cone motility and intracellular ROS in vitro and developing zebrafish embryos for imaging and manipulating
axonal development in vivo. In vitro growth cone guidance assays, novel fluorescent dyes and biosensors
specific for hydrogen peroxide and Src activity, respectively, advanced imaging techniques, chimeric analysis of
Nox2-deficient zebrafish lines as well as retinal ganglion cell-specific Nox2-mutant fish lines will be used to
address the following two Specific Aims: (1) The first aim is to determine the cellular and molecular mechanism
by which ROS in control neurite growth. (2) The second aim is to determine the role of neuronal Nox2 in axonal
pathfinding of retinal ganglion cells. The proposed work is highly innovative because it investigates ROS as a
novel group of signaling molecules in axonal growth and guidance and develops several new zebrafish lines
suitable for studying Nox function in the nervous system. In summary, these studies have the potential of leading
to breakthrough findings in the field of neuronal development and regeneration. Furthermore, since basic
mechanisms of axonal growth and guidance are highly conserved across species, these studies will impact the
development of antioxidant treatments for neurodegenerative diseases and central ne...

## Key facts

- **NIH application ID:** 10033080
- **Project number:** 1R01NS117701-01
- **Recipient organization:** PURDUE UNIVERSITY
- **Principal Investigator:** Daniel Marcel Suter
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $335,649
- **Award type:** 1
- **Project period:** 2020-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10033080

## Citation

> US National Institutes of Health, RePORTER application 10033080, NADPH oxidase regulates growth cone guidance (1R01NS117701-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10033080. Licensed CC0.

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