# Somatodendritic Inhibition of Oligodendrocyte Myelination

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $291,484

## Abstract

PROJECT SUMMARY
An underappreciated aspect of myelination is the avoidance of selecting non-axonal targets. Oligodendrocytes
(OLs) select axons while avoiding neuronal somata, dendrites and processes of other glial cells. How is this
specificity accomplished? While OLs are capable of myelinating permissive structures (artificial fibers and
beads) in the absence of molecular cues, structurally permissive neuronal somata and dendrites remain
unmyelinated. These observations suggest that myelin substrate selection is not cell-intrinsically limited to
physiologically relevant geometries. OL cell processes are likely sensitive to cell-extrinsic cues that ensure the
selection of axons with high fidelity. Utilizing a novel purified spinal cord neuron-OL myelinating coculture
system we find that disruption of dynamic neuron-OL signaling by chemical crosslinking results in aberrant
myelination of the somatodendritic compartment of neurons. In this proposal, we hypothesize that
inhibitory somatodendritic cues act as repulsive membrane signals that are necessary and sufficient to
prevent non-axonal myelination. In this proposal we will: 1. Perform next-generation sequencing and
candidate profiling of membrane proteins expressed exclusively in purified spinal cord neurons. 2. Identify,
confirm and validate expression and localization of repulsive membrane proteins enriched in the
somatodendritic compartment. 3. Investigate the necessity and sufficiency of the repulsive signal(s) to prevent
aberrant myelination and identify receptor(s) on OPCs that mediate the inhibition. Our preliminary data
identifies the Junctional Adhesion Molecule 2 (JAM2), expressed on the somata and dendrites of spinal
cord neurons, as a repulsive signal that inhibits aberrant oligodendrocyte myelination. Taken together,
we propose a model in which broadly indiscriminate myelination is tailored by inhibitory signaling to meet local
myelination requirements.

## Key facts

- **NIH application ID:** 9857499
- **Project number:** 5R01NS097428-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Jonah R Chan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $291,484
- **Award type:** 5
- **Project period:** 2016-06-01 → 2021-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9857499

## Citation

> US National Institutes of Health, RePORTER application 9857499, Somatodendritic Inhibition of Oligodendrocyte Myelination (5R01NS097428-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9857499. Licensed CC0.

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