# Mechanisms of Axon-Schwann cell interactions

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2024 · $373,450

## Abstract

In the vertebrate peripheral nervous system (PNS), specialized glial cells called Schwann cells form the myelin
sheath, which is required for fast action potential propagation as well as neuronal health and survival. The
importance of myelin in normal nervous system function is perhaps best underscored by myelin loss and
inefficient remyelination of axon tracts observed in diseases such as demyelinating peripheral neuropathies.
Such disruptions of myelin can lead to permanent neuron loss, significant pain and morbidity, and ultimately
paralysis. Currently, no treatments exist to prevent demyelination or to enhance remyelination, in part because
of our incomplete understanding of the genetic and molecular control of myelination.
To identify new regulators of myelinating glial cell development, we previously performed a large-scale forward
genetic screen in zebrafish. Through this screen, we identified new mutants in dedicator of cytokinesis (dock1)
and previously showed that these global mutants exhibit severe defects in radial sorting and reduced
myelination in the PNS during development. Moreover, our preliminary analyses suggest a critical function for
Dock1 in nerve repair following injury in adult zebrafish. Dock1 encodes a highly conserved atypical guanine
nucleotide exchange factor that can activate the small Rho GTPase Rac1. To date, no role for Dock1 function
in Schwann cells has been described, although Rac1 is a known regulator of Schwann cell development. Here,
we propose to use zebrafish and mouse models to dissect the mechanisms by which Dock1 controls PNS
development and repair. We aim to define the function of Dock1 in Schwann cells (Aim 1), uncover pathways
up- and downstream of Dock1 function (Aim 2), and test if Dock1 is required for myelin maintenance or repair
following nerve injury in the mammalian PNS (Aim 3). Together, these experiments will define fundamental
mechanisms underlying axon-Schwann cell interactions in development, injury, and repair and can lay the
foundation for new therapies to treat human neuropathies and peripheral nerve damage.

## Key facts

- **NIH application ID:** 10844455
- **Project number:** 5R01NS120651-04
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Kelly R Monk
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $373,450
- **Award type:** 5
- **Project period:** 2021-07-15 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10844455

## Citation

> US National Institutes of Health, RePORTER application 10844455, Mechanisms of Axon-Schwann cell interactions (5R01NS120651-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10844455. Licensed CC0.

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