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

> **NIH NIH R37** · DUKE UNIVERSITY · 2024 · $746,785

## Abstract

Abstract
In the developing nervous system, highly polarized and elongated cells exhibit spatial segregation of cellular
functions. This is exemplified by radial glia cells (RGCs), which are the neural stem cells that generate neurons
and glia in the developing cerebral cortex. RGCs have a basal process extending hundreds of micrometers in
mice, or centimeters in humans, to form basal endfeet at the pia. These basal endfeet reside in a distinct niche
composed of meninges, excitatory and inhibitory neurons. Notably endfeet are proposed to act as antennas
relaying signals. Endfoot integrity is essential for neuronal organization and is linked to several
neurodevelopmental disorders. Yet, despite their importance, remarkably little is known about this subcellular
compartment of radial glia and its role in signaling at the niche. This proposal aims to elucidate fundamental
mechanisms by which RGCs signal and organize the pial niche during brain development. We focus on our
recent discovery that mRNAs are actively transported within RGCs, and localized to endfeet where they can be
locally translated. In the first funding cycle of this grant, we discovered endfeet contain a rich local transcriptome
and subcellular proteome. Functional interrogation of four localized transcripts showed converging requirements
for RGC morphology and interneuron organization. We also developed new tools to propel our understanding of
how RNA localization and local translation influences RGCs. Together, this establishes a novel tractable in vivo
paradigm for investigating local gene regulation in vivo during cortical neurogenesis. In this proposal we will
implement our new molecular tools and apply our unique expertise to address 3 interrelated questions: 1) What
is the molecular composition of RGC endfeet across development and how does this diverge in mouse and
human brains? 2) How does local translation in RGCs impact signaling at the niche? 3) How is local information
relayed within RGC basal structures? Successfully completed, we will have significantly advanced our
understanding of fundamental molecular mechanisms of cortical neurogenesis, and specifically how subcellular
compartments of neural stem cells mediate local gene expression and signaling. More broadly, we will gain
insights into mRNA localization and translation in the developing nervous system.

## Key facts

- **NIH application ID:** 10978922
- **Project number:** 2R37NS110388-06
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Debra L. Silver
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $746,785
- **Award type:** 2
- **Project period:** 2018-09-01 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10978922

## Citation

> US National Institutes of Health, RePORTER application 10978922, Distal mRNA localization and translation in neural stem cells of the developing brain (2R37NS110388-06). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10978922. Licensed CC0.

---

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