Evidence map›Paper›PMID 40374608›Full record

ArticleNature communications2025

Sex-specific perturbations of neuronal development caused by mutations in the autism risk gene DDX3X.

Adele Mossa, Lauren Dierdorff, Jeronimo Lukin, Marta Garcia-Forn, Wei Wang, Fatemeh Mamashli, Yeaji Park, Chiara Fiorenzani, Zeynep Akpinar, Janine Kamps and 3 more

Abstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Adele MossaSeaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Lauren Dierdorff *Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Jeronimo Lukin *Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.ORCID http://orcid.org/0000-0002-2284-7152
Marta Garcia-FornSeaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Wei WangAppel Alzheimer's Disease Research Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY10021, USA.
Fatemeh MamashliDepartment Biochemistry of Neurodegenerative Diseases, Institute of Biochemistry and Pathobiochemistry, Ruhr University Bochum, Bochum, Germany.
Yeaji ParkSeaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Chiara FiorenzaniSeaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Zeynep AkpinarSeaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Janine KampsDepartment Biochemistry of Neurodegenerative Diseases, Institute of Biochemistry and Pathobiochemistry, Ruhr University Bochum, Bochum, Germany.ORCID http://orcid.org/0000-0002-4930-3868
Jörg TatzeltDepartment Biochemistry of Neurodegenerative Diseases, Institute of Biochemistry and Pathobiochemistry, Ruhr University Bochum, Bochum, Germany.ORCID http://orcid.org/0000-0001-5017-5528
Zhuhao WuAppel Alzheimer's Disease Research Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY10021, USA.ORCID http://orcid.org/0000-0002-2471-0555
Silvia De RubeisSeaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. silvia.derubeis@mssm.edu.ORCID http://orcid.org/0000-0001-9383-6883

Funding

Cellular and molecular determinants of DDX3X syndromeR01HD104609 · NICHD · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI DE RUBEIS, SILVIA · 2021 to 2025
$2.8M
Global mapping of altered neural circuits in a mouse model of DDX3X mutationsR01MH131537 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI DE RUBEIS, SILVIA, WU, ZHUHAO · 2023 to 2025
$2.5M
Interdisciplinary Training in Systems and Developmental Biology and Birth DefectsT32HD075735 · NICHD · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI JABS, ETHYLIN WANG · 2013 to 2022
$1.8M
6500 QTrap Mass Spectrometer for Yale UniversityS10OD018034 · OD · YALE UNIVERSITY · PI MANE, SHRIKANT M · 2014 to 2014
$514k
Investigating DDX3X as a sex-specific translational regulator associated with intellectual disabilityR21HD097561 · NICHD · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI DE RUBEIS, SILVIA · 2019 to 2020
$466k
An Ultra-Performance Liquid Chromatography System to Support Metabolomics at Yale UniversityS10OD019967 · OD · YALE UNIVERSITY · PI LAM, TUKIET T · 2015 to 2015
$135k
Deutsche Forschungsgemeinschaft (German Research Foundation) EXC 2033 - 390677874 - RESOLV and TA 167/6-3NICHD NIH HHS R01 HD104609NICHD NIH HHS R21 HD097561NICHD NIH HHS T32 HD075735NIH HHS S10 OD018034NIH HHS S10 OD019967NIMH NIH HHS R01 MH131537U.S. Department of Health & Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) R01HD104609U.S. Department of Health & Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) T32HD075735U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) R01MH131537
6 · The paper itself

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.

Indexed as

Autism Spectrum DisorderAutistic DisorderDEAD-box RNA HelicasesMutationNeurogenesisNeuronsAnimalsBrainCell NucleolusDendritic SpinesDisease Models, AnimalFemaleHumansMaleMiceMice, Inbred C57BLDDX3X protein, humanDdx3x protein, mouseDEAD-box RNA HelicasesRNA, Ribosomal

Identifiers

PMID40374608
PMCPMC12081640

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.