The RNA helicase DDX3 induces neural crest by promoting AKT activity

Area of Science:

• Developmental Biology
• Genetics
• Molecular Biology

Background:

• Mutations in RNA helicase DDX3 are a common cause of human intellectual disability.
• Individuals with DDX3 mutations often exhibit craniofacial and neural crest (NC)-derived cell defects.
• The precise role of DDX3 in NC development remains largely unexplored.

Purpose of the Study:

• To investigate the role of DDX3 in neural crest (NC) induction and craniofacial morphogenesis.
• To elucidate the molecular mechanisms by which DDX3 influences NC development.
• To establish a link between DDX3 function and NC-related birth defects.

Main Methods:

• Utilized *Xenopus tropicalis* as a model organism.
• Employing gene depletion techniques to assess DDX3 function.
• Investigated downstream signaling pathways including AKT, GSK3β, β-catenin, Snai1, and RAC1.

Main Results:

• DDX3 is essential for normal NC induction and craniofacial development in *Xenopus tropicalis*.
• DDX3 depletion impairs AKT kinase activity and reduces β-catenin and Snai1 levels via GSK3β.
• DDX3's RNA helicase activity regulates RAC1 translation, mediating its signaling function in NC induction.

Conclusions:

• DDX3 plays a conserved role in NC development by promoting AKT activity.
• DDX3 regulates NC induction through a signaling cascade involving AKT, GSK3β, and RAC1.
• This study provides a molecular mechanism for NC-related birth defects associated with DDX3 mutations.