# Mechanisms of Developmental Myelination

> **NIH NIH R35** · UNIVERSITY OF COLORADO DENVER · 2021 · $859,072

## Abstract

PROJECT SUMMARY
The long-term goal of this research program is to understand how specific axons of the developing central
nervous system (CNS) are ensheathed with specific amounts of myelin, a specialized, proteolipid-rich
membrane produced by oligodendroglia. During development, subpopulations of neural progenitors produce
oligodendrocyte precursor cells (OPCs), which migrate and divide to populate the CNS. Subsequently, some
OPCs differentiate as myelinating oligodendrocytes whereas other OPCs persist through adulthood.
Importantly, myelin is plastic and can be modified by brain activity. Recent evidence indicates that changes in
OPC proliferation, oligodendrocyte differentiation, myelin sheath characteristics and axon selection for
myelination contribute to myelin plasticity. However, the molecular mechanisms that regulate myelination,
particularly in response to neuronal activity, are poorly understood. The investigations that comprise this
research program focus on three broad areas of developmental myelination. First, using single cell RNA-seq
data we generated, we will investigate how neural progenitors are specified as OPCs. Second, will axo-glial
interactions and mRNA localization promote myelin sheath growth. Third, we will investigate how microglia, the
resident innate immune cells of the CNS, modify myelin coverage on axons in response to neuronal activity.
We use zebrafish as a model system, which enables us to combine time-lapse imaging with genetic and
pharmacological manipulations to observe and test cell behaviors and myelination in an intact, living animal.
The results of this research program have the potential to provide important new insights to the developmental
basis of 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:** 10236984
- **Project number:** 1R35NS122191-01
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Bruce H Appel
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $859,072
- **Award type:** 1
- **Project period:** 2021-05-15 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10236984

## Citation

> US National Institutes of Health, RePORTER application 10236984, Mechanisms of Developmental Myelination (1R35NS122191-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10236984. Licensed CC0.

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