# Epitranscriptomic Control of Local Gene Expression in Neural Stem Cells

> **NIH NIH R21** · DUKE UNIVERSITY · 2020 · $197,748

## Abstract

Abstract
 During brain development, neurons are generated from neural stem cells, also called radial glial
cells (RGCs). These cells exhibit a unique morphology with a long basal process that extends to the
pia to form endfeet. Basal processes serve critical roles as scaffolds for neuronal migration and can
also influence neurogenesis. Despite their importance for neurodevelopment, our understanding of
molecular regulation within these basal radial glial structures remains poor. Our group recently
discovered that RGC endfeet contain a specific transcriptome which can be locally translated. This
suggests that local transcriptomic regulation is important for controlling gene expression in RGCs.
However, our understanding of post-transcriptional mechanisms that regulate mRNAs within RGCs is
very limited. Recently, methylation of adenosine residues in RNA (m6A) has emerged as a pervasive
feature of the transcriptome which plays important roles in the regulation of gene expression. m6A is
particularly abundant within the brain, and recent studies have shown that dynamic methylation enables
cells to fine-tune the expression of subsets of the transcriptome. Moreover, the m6A methyltransferase,
METTL3, is essential for promoting differentiation of stem cells, including RGCs. Our preliminary data
indicate that m6A is present in the local transcriptome of RGC endfeet, suggesting the intriguing but
untested possibility that mRNA methylation controls sub-cellular events in this important stem cell
population. This proposal will test the novel hypothesis that RGC subcellular compartments contain
distinct repertoires of methylated mRNAs and that mRNA modifications contribute to local gene
expression regulation in the developing brain. We will first employ novel methods developed by our
group for RGC endfeet isolation coupled with global m6A mapping strategies to identify the local
methylome in RGCs. We will determine the transcripts whose localization to endfeet is dependent upon
m6A and test the impact of RNA methylation upon local translation. We will additionally test the
hypothesis that FMRP influences endfeet localization by binding m6A. Discoverying how FMRP targets
RNAs in RGCs is important given that FMRP mutation influences cortical development and causes
Fragile X syndrome. Collectively, these studies will provide the first identification of m6A-containing
mRNAs in RGC endfeet and will uncover the transcripts for which local expression in RGCs is m6A-
dependent. This work will provide a foundation for future studies designed to investigate the
consequences of local RGC mRNA regulation on neural stem cell function and brain development.

## Key facts

- **NIH application ID:** 9856487
- **Project number:** 5R21MH119813-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Kathryn D Meyer
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $197,748
- **Award type:** 5
- **Project period:** 2019-02-01 → 2021-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9856487

## Citation

> US National Institutes of Health, RePORTER application 9856487, Epitranscriptomic Control of Local Gene Expression in Neural Stem Cells (5R21MH119813-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9856487. Licensed CC0.

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