ArticleNature communications2025
Sex-specific perturbations of neuronal development caused by mutations in the autism risk gene DDX3X.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Uncoupling memory impairments from autism-associated behaviors in Chd2 deficient mice.Molecular psychiatry · 2026Article
- Sex-linked helicases DDX3X and DDX3Y regulate G-quadruplex-associated stress in neurons.Cell death & disease · 2026Article
- Dissecting the shared genetic architecture between testosterone traits and attention-deficit/hyperactivity disorder.European child & adolescent psychiatry · 2026Article
- Using combined RNA/DNA short read sequencing to investigate allele-specific expression from the inactive X chromosome in human cells.bioRxiv : the preprint server for biology · 2026Article
- Article
- Knockdown of Ddx3x in mPFC induces autistic-like phenotype in mice via altered synaptic plasticity.Translational psychiatry · 2026Article
- Exome Sequencing Resolving a Complex Pediatric Neurodevelopmental Disorder After Inconclusive Prenatal Testing: A Case Report.Children (Basel, Switzerland) · 2026Article
- Cell type-dependent suppression of the RNA helicase DDX3Y levels by the close paralog DDX3X.Frontiers in cell and developmental biology · 2026Article
- Exploration of a DDX3X Gene Supplementation Therapy Including Expanded Characterization and Novel Findings of Sleep Disturbances inBiological psychiatry global open science · 2025Article
- Impaired cortical development and translational control in a missense mouse model of DDX3X syndrome.Disease models & mechanisms · 2025Article
- DNA O-MAP uncovers the molecular neighborhoods associated with specific genomic loci.bioRxiv : the preprint server for biology · 2025Article
- Expanding the understanding of DDX3X-related neurodevelopmental disorder in males.European journal of human genetics : EJHG · 2025Article
- A subpopulation of cortical neurons altered by mutations in the autism risk gene DDX3X.Biology open · 2025Article
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Authors and funding
13 authors.
Funding
Abstract
DDX3X is an X-linked RNA helicase that escapes X chromosome inactivation and is expressed at higher levels in female brains. Mutations in DDX3X are associated with intellectual disability (ID) and autism spectrum disorder (ASD) and are predominantly identified in females (DDX3X syndrome). Using cellular and mouse models, we show that Ddx3x mediates sexual dimorphisms in brain development at a molecular, cellular, and behavioral level. During cortical neuronal development, Ddx3x sustains a female-biased signature of enhanced ribosomal biogenesis and mRNA metabolism. Compared to male neurons, female neurons display larger nucleoli, higher expression of a set of ribosomal proteins, and a higher cytoplasm-to-nucleus ratio of ribosomal RNA. All these sex dimorphisms are obliterated by Ddx3x loss. Ddx3x regulates dendritic arborization complexity in a sex- and dose-dependent manner in both female and male neurons. Ddx3x modulates the development of dendritic spines but only in female neurons. Further, ablating Ddx3x conditionally in forebrain neurons is sufficient to yield sex-specific changes in developmental outcomes and motor function. Together, these findings pose Ddx3x as a mediator of sexual differentiation during neurodevelopment and open new avenues to understand sex differences in health and disease.
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Registered trials
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