# Mechanisms guiding axon selection for myelination in vivo

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2020 · $357,045

## Abstract

PROJECT SUMMARY
The long-term goal of this project is to understand how oligodendrocytes, which are glial cells of the central
nervous system, ensheath specific axons with specialized, proteolipid-rich myelin membrane. To myelinate
axons, oligodendrocytes extend numerous membrane processes than spirally wrap axons. However, not all
axons are myelinated, and myelinated axons can be covered with different amounts of myelin. Based on
observations that brain activity can modify myelin, we hypothesize that signals from axons are communicated to
oligodendrocyte processes to direct axon ensheathment and myelination. Using zebrafish as a model system,
this project combines in vivo live cell imaging with genetic, optogenetic and pharmacological manipulations to
investigate mechanisms that guide formation of myelin on specific axons during development. Specific Aim 1 will
test the hypothesis that canonical synaptic proteins mediated axon-oligodendrocyte interactions to regulate
myelin sheath formation and growth. Specific Aim 2 will use in vivo imaging of mTOR signaling activity combined
with genetic, optogenetic and pharmacological approaches to test the hypothesis that intrasheath mTOR
signaling mediates axonal signals to control translation. Completion of these aims will substantially extend our
understanding of the cellular and molecular mechanisms by which oligodendrocytes ensheath axons with
specific amounts of myelin during development and reveal how neuronal activity might modify axonal myelination.
The results of this project have the potential for important new insights to learning, memory and psychiatric
disease and to provide a foundation for designing therapeutic strategies to promote myelination of brains
damaged by disease or injury.

## Key facts

- **NIH application ID:** 10049402
- **Project number:** 2R01NS095679-06
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Bruce H Appel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $357,045
- **Award type:** 2
- **Project period:** 2015-09-15 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10049402

## Citation

> US National Institutes of Health, RePORTER application 10049402, Mechanisms guiding axon selection for myelination in vivo (2R01NS095679-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10049402. Licensed CC0.

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