# Mechanisms of Neural Crest Induction and Craniofacial Disorders

> **NIH NIH R01** · UNIVERSITY OF DELAWARE · 2024 · $364,766

## Abstract

Summary/Abstract
Aberrant development of the multipotent neural crest (NC) cells can result in some of the most common
birth defects called neurocristopathies, including malformations of craniofacial structures, dental tissues,
and the peripheral nervous system. In humans, mutations in the RNA helicase DDX3 cause intellectual
disability with multiple potential neurocristopathies; however, the function of DDX3 in NC development is
unknown. In Xenopus tropicalis, a highly tractable model for studying NC development, depletion of DDX3
downregulates the AKT kinase activity and Wnt/beta-catenin signaling, leading to reduced NC induction.
The goal of this application is to elucidate how DDX3 and downstream signaling molecules function in NC
induction. The central hypothesis is that DDX3 induces the NC through a downstream gene regulatory
network, whose components are critical for normal NC induction. This application has three specific aims.
The first aim will determine how DDX3 induces the NC, with a focus on understanding how DDX3 activates
AKT. The second aim will investigate the roles of AKT in NC induction downstream of DDX3, and the
hypothesis to be tested is that AKT functions through Wnt/beta-catenin signaling. The third aim will test the
feasibility of using X. tropicalis as a model to study how diseases-associated human mutations in DDX3
and downstream genes affect cell signaling and NC induction. Outcomes of this proposed research should
provide new insight into the fundamental mechanisms governing NC induction, as well as the etiology of
human neurocristopathies caused by mutations in multiple genes in this network.

## Key facts

- **NIH application ID:** 10824282
- **Project number:** 5R01DE029802-05
- **Recipient organization:** UNIVERSITY OF DELAWARE
- **Principal Investigator:** Shuo Wei
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $364,766
- **Award type:** 5
- **Project period:** 2020-07-17 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10824282

## Citation

> US National Institutes of Health, RePORTER application 10824282, Mechanisms of Neural Crest Induction and Craniofacial Disorders (5R01DE029802-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10824282. Licensed CC0.

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