Evidence map›Paper›PMID 40498903›Full record

ArticleBrain : a journal of neurology2025

POU3F2 regulates canonical Wnt signalling via SOX13 and ADNP to expand the neural progenitor population.

Courtney R Benoit, Lilia B Sattler, Aimee J Aylward, Olivia Pembridge, Bella Kim, Christina R Muratore, Meichen Liao, Amy He, Nancy Ashour, Seeley B Fancher and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Brain : a journal of neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Courtney R BenoitAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Lilia B SattlerAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Aimee J AylwardAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Olivia PembridgeAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Bella KimAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Christina R MuratoreAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Meichen LiaoAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Amy HeAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Nancy AshourAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Seeley B FancherAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Alexandra M LishAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Richard V PearseAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Joseph D BuxbaumDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Tracy L Young-PearseAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.

Funding

Probing Heterogeneity of Alzheimer's Disease Using iPSCsR01AG055909 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI Tracy L YOUNG-PEARSE · 2018 to 2026
$5.7M
Genes and developmental signaling pathways in neuropsychiatric disordersR01MH101148 · NIMH · BRIGHAM AND WOMEN'S HOSPITAL · PI YOUNG-PEARSE, TRACY L · 2014 to 2018
$2.5M
1/4 - The Autism Sequencing Consortium: Discovering autism risk genes and how they impact core features of the disorderR01MH129724 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Joseph D. Buxbaum · 2022 to 2026
$2.0M
3/4 The Autism Sequencing Consortium: Discovering autism risk genes and how they impact core features of the disorderR01MH129725 · NIMH · CARNEGIE-MELLON UNIVERSITY · PI KATHRYN M ROEDER · 2022 to 2026
$1.9M
4/4 - The Autism Sequencing Consortium: Discovering autism risk genes and how they impact core features of the disorderR01MH129751 · NIMH · UNIVERSITY OF OXFORD · PI Stephan Sanders · 2022 to 2026
$1.4M
Dauten Family FoundationHarvard Brain Science Initiative Bipolar Disorder Seed GrantNIA NIH HHS R01 AG055909NIH HHS R01AG055909NIH HHS RO1MH101148NIMH NIH HHS R01 MH101148NIMH NIH HHS R01 MH129724NIMH NIH HHS R01 MH129725NIMH NIH HHS R01 MH129751
6 · The paper itself

Abstract

Loss-of-function mutations in the transcription factor POU3F2 have been identified in individuals with neurodevelopmental disorders. To elucidate the mechanistic role of POU3F2 in human neurodevelopment, we induced POU3F2 disruption in human neural progenitor cells (NPCs). Mutation of POU3F2 in NPCs causes reduced baseline canonical Wnt signalling and decreased proliferation, resulting in premature specification of radial glia. Additionally, POU3F2 levels across genetically diverse NPCs significantly associate positively with baseline canonical Wnt signalling and negatively with markers of radial glia specification. Through a series of unbiased analyses, we show that SRY-box transcription factor 13 (SOX13) and activity dependent neuroprotector homeobox (ADNP) are transcriptional targets of POU3F2 which mediate POU3F2's effects on Wnt signalling in human NPCs. Finally, we describe five individuals with autism spectrum disorder that harbour loss-of-function mutations in POU3F2, enhancing the genetic evidence for its critical role in human neurodevelopment. Together, these studies define POU3F2 as an activator of canonical Wnt signalling and mechanistically link two high-confidence autism genes, ADNP and POU3F2, in the regulation of neurodevelopment.

Indexed as

Homeodomain ProteinsNerve Tissue ProteinsNeural Stem CellsOctamer Transcription Factor-3POU Domain FactorsWnt Signaling PathwayAutism Spectrum DisorderFemaleHumansMaleHomeodomain ProteinsNerve Tissue ProteinsOctamer Transcription Factor-3POU Domain Factorstranscription factor Brn-2autism spectrum disorder (ASD)canonical Wnt signallingCRISPR/Cas9induced pluripotent stem cells (iPSCs)neural progenitor cells (NPCs)neurodevelopmental disorders

Identifiers

PMID40498903
PMCPMC12677912

What OpenQuestion holds

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LicenceCC BY
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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 OpenQuestion graph.