# Mechanisms of neuron-oligodendrocyte precursor cell interactions

> **NIH NIH R21** · OREGON HEALTH & SCIENCE UNIVERSITY · 2021 · $231,000

## Abstract

The myelin sheath is a multilayered membrane generated by specialized glial cells called oligodendrocytes
(OLs) that iteratively spiral their plasma membranes around axon segments in the vertebrate central nervous
system (CNS). OLs derive from OL precursor cells (OPCs), and functional interactions between neurons and
OLs as well as between neurons and OPCs are critical for CNS function and health. A specialized but very
poorly understood interaction between neurons and OPCs occurs at the neuron-OPC synapse: nearly all
OPCs form synapses postsynaptically to neurons. OPCs differ from mature neurons in many ways: they
migrate, frequently remodel processes, and are capable of transforming their processes into myelin sheaths.
These unique cellular features raise questions as to whether neuron-OPC synapses adapt to an OPC's unique
biology and employ distinct mechanisms for synapse development. Despite previous EM and
electrophysiological characterizations, almost nothing is known about synapse development in OPCs, the
molecular mechanisms that govern neuron-OPC synapse formation, and how signaling via neuron-OPC
synapses influences myelination.
Here we propose to use zebrafish to investigate neuron-OPC synapse development, the relationship of these
synapses to myelination, and to probe the underlying molecular mechanisms regulating these processes.
Zebrafish provide unparalleled optical clarity for in vivo imaging and powerful tools for rapid genetic
manipulations. We have identified the presence of two postsynaptic scaffolds, PSD-95 and gephyrin, at
neuron-OPC synapses and generated new tools to label synapses containing these scaffolds in OPCs. Our
preliminary results suggest unique synapse assembly and disassembly mechanisms in OPCs and highlight
potential roles for synapses in OPC development and myelination. In this application, we will determine if and
how neuron-OPC synapses are correlated with OPC differentiation and subsequent myelination (Aim 1). We
will also employ cell-specific knockdown approaches to identify genes that are critical for synapse development
and assess their roles in OPC biology (Aim 2). Together, our work can define previously unknown functions for
neuron-OPC synapses and reveal important mechanisms that mediate neuron-glial interactions in the
vertebrate CNS.

## Key facts

- **NIH application ID:** 10153390
- **Project number:** 1R21NS120650-01
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Kelly R Monk
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $231,000
- **Award type:** 1
- **Project period:** 2020-12-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10153390

## Citation

> US National Institutes of Health, RePORTER application 10153390, Mechanisms of neuron-oligodendrocyte precursor cell interactions (1R21NS120650-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10153390. Licensed CC0.

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