# The role of an Intellectual Disability gene, DDX3X, in neural progenitors during brain development

> **NIH NIH F32** · DUKE UNIVERSITY · 2021 · $32,997

## Abstract

Abstract:
Mutations in the RNA helicase DDX3X are associated with a wide range of developmental deficits and
brain malformations and account for 1-3% of Intellectual disability (ID) cases in females. Interestingly,
expression of DDX3X mutants induces stress granule-like complexes, an RNA-protein assembly associated
with neurological diseases. Our preliminary data indicate DDX3X regulates neural progenitor proliferation
and their propensity to form neurons. However, the distinct requirements for DDX3X in neural
progenitors and neurons have not been characterized nor the mechanisms by which ID-associated
DDX3X mutations impair cortical development. Here, we test the hypothesis that DDX3X controls
neural progenitor proliferation and fate decisions through regulation of translation and SG
dynamics. Aim 1 uses mouse models to define the distinct consequences of Ddx3x depletion in progenitors
and neurons during cortical development. Aim 2 employs translation-based assays to understand how
DDX3X translational control impacts progenitor proliferation. Aim 3 seeks to characterize the nature of
DDX3X ID-mutant granules and the protein interactome of WT DDX3X and ID-mutants. Upon completion,
this proposal will enhance our understanding of post-transcriptional RNA regulation required for normal
brain development and the mechanism by which aberrations can lead to ID.

## Key facts

- **NIH application ID:** 10395855
- **Project number:** 3F32NS112566-02S1
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Mariah Lawler Hoye
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $32,997
- **Award type:** 3
- **Project period:** 2019-09-01 → 2022-05-20

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10395855

## Citation

> US National Institutes of Health, RePORTER application 10395855, The role of an Intellectual Disability gene, DDX3X, in neural progenitors during brain development (3F32NS112566-02S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10395855. Licensed CC0.

---

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