Evidence map›Paper›PMID 40398411›Full record

ArticleNeuron2025

Multimodal analyses reveal genes driving electrophysiological maturation of neurons in the primate prefrontal cortex.

Yu Gao, Qiping Dong, Kalpana Hanthanan Arachchilage, Ryan D Risgaard, Moosa Syed, Jie Sheng, Danielle K Schmidt, Ting Jin, Shuang Liu, Soraya O Sandoval and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuron, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Single-nucleus analysis reveals oxidative stress in Down syndrome basal forebrain neurons at birth.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  6. Article
  7. Evolution is in the details: Regulatory differences in modern human and Neanderthal.Computational and structural biotechnology journal · 2025
    Article
  8. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors.

Yu GaoWaisman Center, University of Wisconsin-Madison, Madison, WI 53705, USA; Department of Neuroscience, University of Wisconsin-Madison, Madison, WI 53705, USA.
Qiping DongWaisman Center, University of Wisconsin-Madison, Madison, WI 53705, USA.
Kalpana Hanthanan ArachchilageWaisman Center, University of Wisconsin-Madison, Madison, WI 53705, USA.
Ryan D RisgaardWaisman Center, University of Wisconsin-Madison, Madison, WI 53705, USA; Department of Neuroscience, University of Wisconsin-Madison, Madison, WI 53705, USA.
Moosa SyedWaisman Center, University of Wisconsin-Madison, Madison, WI 53705, USA; Department of Neuroscience, University of Wisconsin-Madison, Madison, WI 53705, USA.
Jie ShengWaisman Center, University of Wisconsin-Madison, Madison, WI 53705, USA.
Danielle K SchmidtWaisman Center, University of Wisconsin-Madison, Madison, WI 53705, USA; Department of Neuroscience, University of Wisconsin-Madison, Madison, WI 53705, USA.
Ting JinWaisman Center, University of Wisconsin-Madison, Madison, WI 53705, USA.
Shuang LiuWaisman Center, University of Wisconsin-Madison, Madison, WI 53705, USA.
Soraya O SandovalWaisman Center, University of Wisconsin-Madison, Madison, WI 53705, USA; Department of Neuroscience, University of Wisconsin-Madison, Madison, WI 53705, USA; Neuroscience Training Program, University of Wisconsin-Madison, Madison, WI 53705, USA.
Sara KnaackWaisman Center, University of Wisconsin-Madison, Madison, WI 53705, USA; Department of Neuroscience, University of Wisconsin-Madison, Madison, WI 53705, USA.
Magnus T EckholmWaisman Center, University of Wisconsin-Madison, Madison, WI 53705, USA; Department of Neuroscience, University of Wisconsin-Madison, Madison, WI 53705, USA.
Rachel J ChenWaisman Center, University of Wisconsin-Madison, Madison, WI 53705, USA; Department of Neuroscience, University of Wisconsin-Madison, Madison, WI 53705, USA.
Yu GuoWaisman Center, University of Wisconsin-Madison, Madison, WI 53705, USA; Department of Neuroscience, University of Wisconsin-Madison, Madison, WI 53705, USA.
Dan DohertyDepartment of Pediatrics, University of Washington School of Medicine, Seattle, WA 98195, USA.
Ian GlassDepartment of Pediatrics, University of Washington School of Medicine, Seattle, WA 98195, USA.
Jon E LevineDepartment of Neuroscience, University of Wisconsin-Madison, Madison, WI 53705, USA; Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53705, USA.
Daifeng WangWaisman Center, University of Wisconsin-Madison, Madison, WI 53705, USA; Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI 53705, USA; Department of Computer Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA. Electronic address: daifeng.wang@wisc.edu.
Qiang ChangWaisman Center, University of Wisconsin-Madison, Madison, WI 53705, USA; Department of Medical Genetics, University of Wisconsin-Madison, Madison, WI 53705, USA; Department of Neurology, University of Wisconsin-Madison, Madison, WI 53705, USA. Electronic address: qchang@waisman.wisc.edu.
Xinyu ZhaoWaisman Center, University of Wisconsin-Madison, Madison, WI 53705, USA; Department of Neuroscience, University of Wisconsin-Madison, Madison, WI 53705, USA. Electronic address: xinyu.zhao@wisc.edu.
Andre M M SousaWaisman Center, University of Wisconsin-Madison, Madison, WI 53705, USA; Department of Neuroscience, University of Wisconsin-Madison, Madison, WI 53705, USA. Electronic address: andre.sousa@wisc.edu.

Funding

WNPRC Supplemental Request for Nonhuman Primate Enclosures to Equip HIV/AIDS-Related Research FacilitiesP51OD011106 · OD · UNIVERSITY OF WISCONSIN-MADISON · PI Dorota A. Grejner-Brzezinska · 2012 to 2026
$150.7M
A Multidisciplinary Center for Developing Human and Non-human Primate Brain Cell AtlasesUM1MH130991 · NIMH · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Hao Huang, ARNOLD KRIEGSTEIN · 2022 to 2026
$25.2M
LABORATORY OF DEVELOPMENTAL BIOLOGYR24HD000836 · NICHD · UNIVERSITY OF WASHINGTON · PI Ian Amos Glass · 1995 to 2026
$16.9M
Understanding the molecular mechanisms that contribute to neuropsychiatric symptoms in Alzheimer DiseaseR01AG067025 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI FINKBEINER, STEVEN M, HAROUTUNIAN, VAHRAM · 2019 to 2023
$11.8M
Supplement to TR01 Human cortical development and neural plasticity altered by trisomy 21R01HD106197 · NICHD · UNIVERSITY OF WISCONSIN-MADISON · PI BHATTACHARYYA, ANITA, ZHANG, SU-CHUN · 2021 to 2025
$11.4M
Waisman Center Intellectual and Developmental Disabilities Research CenterP50HD105353 · NICHD · UNIVERSITY OF WISCONSIN-MADISON · PI Qiang Chang · 2021 to 2026
$8.5M
Integrated Training For Physician-ScientistsT32GM140935 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI Anna Huttenlocher, Jeniel E Nett · 2021 to 2026
$6.5M
Newborn Neurons in the Adult Hippocampal NetworkR01NS064025 · NINDS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI OVERSTREET-WADICHE, LINDA · 2009 to 2023
$5.6M
In Vivo Function of Neuronal Activity-Induced MeCP2 phosphorylationR01HD064743 · NICHD · UNIVERSITY OF WISCONSIN-MADISON · PI CHANG, QIANG · 2010 to 2021
$3.0M
The Role of MDM2 in FMRP regulation of neuronal developmentR01MH116582 · NIMH · UNIVERSITY OF WISCONSIN-MADISON · PI ZHAO, XINYU · 2018 to 2022
$2.2M
The role of RNA binding protein in FXR1P in interneuronsR01MH118827 · NIMH · UNIVERSITY OF WISCONSIN-MADISON · PI ZHAO, XINYU · 2019 to 2023
$2.2M
Interrogate FMRP functions in primate brain developmentR01MH136152 · NIMH · UNIVERSITY OF WISCONSIN-MADISON · PI Xinyu Zhao · 2024 to 2026
$2.2M
NIA NIH HHS R01 AG067025NICHD NIH HHS P50 HD105353NICHD NIH HHS R01 HD064743NICHD NIH HHS R01 HD106197NICHD NIH HHS R24 HD000836NIGMS NIH HHS T32 GM140935NIH HHS P51 OD011106NIMH NIH HHS R01 MH116582NIMH NIH HHS R01 MH118827NIMH NIH HHS R01 MH136152NIMH NIH HHS R36 MH136790NIMH NIH HHS RF1 MH128695NIMH NIH HHS UM1 MH130991NINDS NIH HHS R01 NS064025NINDS NIH HHS R01 NS105200NINDS NIH HHS R01 NS138268
6 · The paper itself

Abstract

The prefrontal cortex (PFC) is critical for myriad high-cognitive functions and is associated with several neuropsychiatric disorders. Here, using Patch-seq and single-nucleus multiomic analyses, we identified genes and regulatory networks governing the maturation of distinct neuronal populations in the PFC of rhesus macaque. We discovered that specific electrophysiological properties exhibited distinct maturational kinetics and identified key genes underlying these properties. We unveiled that RAPGEF4 is important for the maturation of resting membrane potential and inward sodium current in both macaque and human. We demonstrated that knockdown of CHD8, a high-confidence autism risk gene, in human and macaque organotypic slices led to impaired maturation, via downregulation of key genes, including RAPGEF4. Restoring the expression of RAPGEF4 rescued the proper electrophysiological maturation of CHD8-deficient neurons. Our study revealed regulators of neuronal maturation during a critical period of PFC development in primates and implicated such regulators in molecular processes underlying autism.

Indexed as

NeuronsPrefrontal CortexAnimalsDNA-Binding ProteinsHumansMacaca mulattaMaleMembrane PotentialsDNA-Binding ProteinsCHD8functional genomicsneurodevelopmental disorderneuronal maturationnon-human primatePatch-seqprefrontal cortexprenatal developmentRAPGEF4single-nucleus multiome

Identifiers

PMID40398411
PMCPMC12331439

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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.