# Distal mRNA localization and translation in neural stem cells of the developing brain

> **NIH NIH R01** · DUKE UNIVERSITY · 2021 · $356,145

## Abstract

Abstract
mRNA localization and local translation are conserved mechanisms enabling spatial and temporal control of
gene expression. These processes are particularly important in the nervous system, where local regulation of
gene expression influences axon guidance and synaptic activity. Much of our understanding of mRNA
localization and local translation has relied upon in vitro studies. We recently established a novel tractable in
vivo paradigm for investigating local gene regulation in vivo in the developing nervous system. Specifically we
found that mRNA is sub-cellularly localized and locally translated in basal structures of embryonic radial glial
cells (RGCs), called endfeet. These basal structures are essential for tissue integrity and neuronal migration,
thus impacting the central function of RGCs in neuron generation. We developed live imaging approaches to
discover that mRNA can be actively transported in RGCs and locally translated in basal endfeet. We also
developed novel methods to isolate RGC endfeet and used these to discover a local transcriptome in endfeet,
bound by the RNA binding protein, FMRP. Our studies lead us to hypothesize that RNA localization and local
translation are intrinsically and extrinsically regulated in RGC endfeet to influence signaling and the
cytoskeleton. In this proposal we aim to implement these new molecular imaging and genomic tools towards:
(1) discovering local transcriptomes of RGC endfeet across development, (2) determining intrinsic and extrinsic
regulation of translation in RGC endfeet, and (3) defining functions for RNA localization in RGC endfeet.
Successfully completed, we will have significantly advanced our understanding of mRNA localization and
translation in the developing nervous system, by studying these processes in an in vivo model.

## Key facts

- **NIH application ID:** 10188661
- **Project number:** 5R01NS110388-04
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Debra L. Silver
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $356,145
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10188661

## Citation

> US National Institutes of Health, RePORTER application 10188661, Distal mRNA localization and translation in neural stem cells of the developing brain (5R01NS110388-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10188661. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*