# The Role of an Intellectual Disability Gene, DDX3X, In Neural Progenitors During Brain Development

> **NIH NIH F32** · DUKE UNIVERSITY · 2020 · $99,033

## 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 in neural cells induces ribonucleoprotein (RNP) granules, which are RNA-protein assemblies
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 that DDX3X-ID mutants
impair RNP interactions. 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 identify key
DDX3X translational targets relevant for progenitor proliferation. Aim 3 characterizes 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 RNA regulation required for normal brain development and the mechanism by
which aberrations can lead to ID.

## Key facts

- **NIH application ID:** 10003040
- **Project number:** 5F32NS112566-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Mariah Lawler Hoye
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $99,033
- **Award type:** 5
- **Project period:** 2019-09-01 → 2022-05-20

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10003040

## Citation

> US National Institutes of Health, RePORTER application 10003040, The Role of an Intellectual Disability Gene, DDX3X, In Neural Progenitors During Brain Development (5F32NS112566-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10003040. Licensed CC0.

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