PXD060033

PXD060033 is an original dataset announced via ProteomeXchange.

Title	Sex specific pertubations of neuronal development caused by mutations in the autism risk gene DDX3X
Description	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. 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 regulates 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.
HostingRepository	PRIDE
AnnounceDate	2025-05-26
AnnouncementXML	Submission_2025-05-25_16:16:06.628.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Silvia De Rubeis
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-01-21 14:04:54	ID requested
⏵ 1	2025-05-25 16:16:07	announced

10.1038/s41467-025-59680-8;

Mossa A, Dierdorff L, Lukin J, Garcia-Forn M, Wang W, Mamashli F, Park Y, Fiorenzani C, Akpinar Z, Kamps J, Tatzelt J, Wu Z, De Rubeis S, Sex-specific perturbations of neuronal development caused by mutations in the autism risk gene DDX3X. Nat Commun, 16(1):4512(2025) [pubmed]

submitter keyword: sex differences

neuronal development

dendritic spines

mRNA translation

motor behavior

autism

DDX3X

nucleolus

ribosome biogenesis

Silvia De Rubeis
contact affiliation	Department of Psychiatry, Seaver Autism Center for Research and Treatment, Mindich Child Health and Development Institute, Friedman Brain Institute, Alper Center for Neural Development and Regeneration, Icahn School of Medicine at Mount Sinai, USA
contact email	silvia.derubeis@mssm.edu
lab head
Silvia De Rubeis
contact affiliation	Icahn School of Medicine at Mount Sinai
contact email	derubeislab@gmail.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/05/PXD060033

PRIDE project URI

• PRIDE
  1. PXD060033
     1. Label: PRIDE project
     2. Name: Sex specific pertubations of neuronal development caused by mutations in the autism risk gene DDX3X