ArticleNeuron2021
Parallel in vivo analysis of large-effect autism genes implicates cortical neurogenesis and estrogen in risk and resilience.
Erratum issuedOpen access · bronzeAbstract read
In one paragraph
Article in Neuron, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 49 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed, 1 pooled it
13.7field-weighted citation impact, top 1% of its field
What it found
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 101 citations in OpenAlex.
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- Social and Anxiety-Like Behaviors Are Affected in Juvenile Mice With Gli2Brain and behavior · 2026Article
- The prenatal sex steroid theory of autism after 25 years.Nature human behaviour · 2026Review
- Assessing circuit function in the developingFrontiers in behavioral neuroscience · 2026Review
- Is maternal diabetes associated with autism spectrum disorder and ADHD in the offspring? A short review.Frontiers in clinical diabetes and healthcare · 2026Review
- Syngap1 and the development of murine neocortical progenitor cells.Nature communications · 2025Article
- Molecular and Genetic Mechanisms in Autism Spectrum Disorder.Annals of neurology · 2025Review
- CRISPR-engineered deletion ofbioRxiv : the preprint server for biology · 2025Article
- Rare coding mutations identify 36 large-effect risk genes in obsessive-compulsive disorder and chronic tic disorders.medRxiv : the preprint server for health sciences · 2025Article
- ZMYND11 functions in bimodal regulation of latent genes and brain-like splicing to safeguard corticogenesis.Nature communications · 2025Article
- Multiple autism genes influence GABA neuron remodeling via distinct developmental trajectories.Genetics · 2025Article
- Sex differences in the developing human cortex intersect with genetic risk of neurodevelopmental disorders.bioRxiv : the preprint server for biology · 2025Article
- Linking autism risk genes to morphological and pharmaceutical screening by high-content imaging: Future directions and opinion.Psychiatry and clinical neurosciences · 2025Review
- Review: Child Psychiatry in the Era of Genomics: The Promise of Translational Genetics Research for the Clinic.JAACAP open · 2025Review
- Adeno-associated viral tools to trace neural development and connectivity across amphibians.Developmental cell · 2025Article
- Autism gene variants disrupt enteric neuron migration and cause gastrointestinal dysmotility.Nature communications · 2025Article
- Chronic exposure to glucocorticoids amplifies inhibitory neuron cell fate during human neurodevelopment in organoids.Science advances · 2025Article
- Convergence of autism proteins at the cilium.bioRxiv : the preprint server for biology · 2025Article
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
18 authors at 3 institutions in 1 country.
Helen Rankin WillseyDepartment of Psychiatry and Behavioral Sciences, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Cameron R T ExnerDepartment of Psychiatry and Behavioral Sciences, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA.
Yuxiao XuDepartment of Psychiatry and Behavioral Sciences, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Amanda EverittDepartment of Psychiatry and Behavioral Sciences, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA; Institute for Neurodegenerative Diseases, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA.
Nawei SunDepartment of Psychiatry and Behavioral Sciences, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA; Institute for Neurodegenerative Diseases, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA.
Belinda WangDepartment of Psychiatry and Behavioral Sciences, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA; Institute for Neurodegenerative Diseases, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA.
Jeanselle DeaDepartment of Psychiatry and Behavioral Sciences, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA.
Galina SchmunkDepartment of Psychiatry and Behavioral Sciences, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA; Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA.
Yefim ZaltsmanDepartment of Psychiatry and Behavioral Sciences, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA; Institute for Neurodegenerative Diseases, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA.
Nia TeerikorpiDepartment of Psychiatry and Behavioral Sciences, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA; Institute for Neurodegenerative Diseases, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA.
Albert KimDepartment of Psychiatry and Behavioral Sciences, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Aoife S AndersonDepartment of Psychiatry and Behavioral Sciences, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA.
David ShinDepartment of Psychiatry and Behavioral Sciences, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA; Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA.
Meghan SeylerDepartment of Psychiatry and Behavioral Sciences, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA; Institute for Neurodegenerative Diseases, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA.
Tomasz J NowakowskiDepartment of Psychiatry and Behavioral Sciences, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA; Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA.
Richard M HarlandDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA. Electronic address: harland@berkeley.edu.
A Jeremy WillseyDepartment of Psychiatry and Behavioral Sciences, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA; Institute for Neurodegenerative Diseases, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: jeremy.willsey@ucsf.edu.
Matthew W StateDepartment of Psychiatry and Behavioral Sciences, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94143, USA; Langley Porter Psychiatric Institute, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: matthew.state@ucsf.edu.
University of California, San Francisco · USQB3 · USUniversity of California, Berkeley · US
Funding
The Psychiatric Cell Map Initiative: Connecting Genomics, Subcellular Networks, and Higher Order PhenotypesU01MH115747 · NIMH · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KAMPMANN, MARTIN, KROGAN, NEVAN J · 2018 to 2022
$19.6MTRAINING THE NEXT GENERATION OF MENTAL HEALTH RESEARCHERSR25MH060482 · NIMH · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI DANIEL H MATHALON, Susan M. Voglmaier · 2000 to 2026
$5.2MGene Expression in Amphibian DevelopmentR35GM127069 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI Richard M Harland · 2018 to 2026
$4.2MMapping Developmental Lineage Relationships in the Cerebral CortexRF1MH121268 · NIMH · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI NOWAKOWSKI, TOMASZ · 2019 to 2019
$2.1MPacific Biosciences PacBio RS Single Molecule Real Time SequencerS10OD018174 · OD · UNIVERSITY OF CALIFORNIA BERKELEY · PI ROKHSAR, DANIEL SOLEYMAN · 2014 to 2014
$600kIdentifying phenotypic convergence among autism spectrum disorder (ASD) genes using CRISPR/Cas9 in XenopusR21MH112158 · NIMH · UNIVERSITY OF CALIFORNIA BERKELEY · PI HARLAND, RICHARD M · 2017 to 2018
$417kNIGMS NIH HHS R35 GM127069NIH HHS S10 OD018174NIMH NIH HHS R21 MH112158NIMH NIH HHS R25 MH060482NIMH NIH HHS RF1 MH121268NIMH NIH HHS U01 MH115747
Abstract
Gene Ontology analyses of autism spectrum disorders (ASD) risk genes have repeatedly highlighted synaptic function and transcriptional regulation as key points of convergence. However, these analyses rely on incomplete knowledge of gene function across brain development. Here we leverage Xenopus tropicalis to study in vivo ten genes with the strongest statistical evidence for association with ASD. All genes are expressed in developing telencephalon at time points mapping to human mid-prenatal development, and mutations lead to an increase in the ratio of neural progenitor cells to maturing neurons, supporting previous in silico systems biological findings implicating cortical neurons in ASD vulnerability, but expanding the range of convergent functions to include neurogenesis. Systematic chemical screening identifies that estrogen, via Sonic hedgehog signaling, rescues this convergent phenotype in Xenopus and human models of brain development, suggesting a resilience factor that may mitigate a range of ASD genetic risks.
Indexed as
NeurogenesisAnimalsAutism Spectrum DisorderCerebral CortexDrug Evaluation, PreclinicalEstrogensFemaleGene Expression Regulation, DevelopmentalHumansMaleRisk FactorsSignal TransductionXenopusEstrogensautism spectrum disordersbrain developmentconvergentCRISPRestrogengeneticsneural progenitor cellsneurogenesissonic hedgehogXenopus tropicalis
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