Deficiency of <i>DDX3X</i> results in neurogenesis defects and abnormal behaviors via dysfunction of the Notch signaling.

ABSTRACT: The molecular mechanisms underlying the neurodevelopmental disorders (NDDs) caused by DDX3X variants remain poorly understood. In this study, we validated that de novo DDX3X variants are enriched in female developmental delay (DD) patients and mainly affect the evolutionarily conserved amino acids based on a meta-analysis of 46,612 NDD trios. We generated a ddx3x deficient zebrafish allele, which exhibited reduced survival rate, DD, microcephaly, adaptation defects, anxiolytic behaviors, social interaction deficits, and impaired spatial recognitive memory. As revealed by single-nucleus RNA sequencing and biological validations, ddx3x deficiency leads to reduced neural stem cell pool, decreased total neuron number, and imbalanced differentiation of excitatory and

SUBMITTER: Duan W 

PROVIDER: S-EPMC11551356 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature