# The RNA Binding Protein FMRP Promotes Myelin Sheath Growth

> **NIH NIH R21** · UNIVERSITY OF COLORADO DENVER · 2020 · $427,625

## Abstract

Project Summary
Cells in the nervous system are highly polarized and intercellular contacts take place at great distance from cell
bodies. Oligodendrocytes produce numerous myelin sheaths on independent axons of variable size and
physiology, which highlights remarkable flexibility in the production of myelin membrane at the tips of individual
distal processes. Moreover, myelination is an activity-dependent process that enhances neuronal function and
is required for learning and memory, indicating essential contributions of oligodendrocytes to neural circuit
development. Interestingly, myelin deficiencies and altered myelin gene expression have been noted in Fragile
X Syndrome, autism spectrum disorders, and a wide array of neurodevelopmental disorders, which indicate
essential roles for oligodendrocytes in disease pathogenesis. Our recent evidence indicates that the RNA
binding protein fragile x mental retardation protein (FMRP) is required for myelin sheath growth in a
mechanism that is dependent on the translational regulation of mRNA. However, the genes coordinating initial
myelin sheath growth are unknown, as are the subcellular mechanisms of mRNA regulation in
oligodendrocytes. We hypothesize that FMRP regulates the localization and translation of mRNAs required for
myelin sheath growth in oligodendrocytes. We will test this hypothesis using zebrafish, building upon our
expertise in cell-type specific visualization and manipulation of gene expression in the developing nervous
system. Our experimental plan has two parts. First, we will identify the precise location of FMRP binding on
target mRNAs. Second, we will visualize the subcellular localization of mRNAs predicted to underlie myelin
sheath growth and manipulate target gene expression specifically in oligodendrocytes of living zebrafish. This
project has the potential to uncover the essential genes required for initial myelin sheath growth and will lay the
foundation for future investigations into the mechanism of subcellular activity-dependent regulation of mRNA
translation during myelination.

## Key facts

- **NIH application ID:** 10039005
- **Project number:** 1R21NS117886-01
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Caleb Andrew Doll
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $427,625
- **Award type:** 1
- **Project period:** 2020-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10039005

## Citation

> US National Institutes of Health, RePORTER application 10039005, The RNA Binding Protein FMRP Promotes Myelin Sheath Growth (1R21NS117886-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10039005. Licensed CC0.

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