ArticleNature neuroscience2022
Impaired neurogenesis alters brain biomechanics in a neuroprogenitor-based genetic subtype of congenital hydrocephalus.
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Article in Nature neuroscience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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63citing papers in PubMed
36.2field-weighted citation impact, top 1% of its field
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Who cites it
63 citing papers in PubMed, 96 citations in OpenAlex.
- Early-onset ventriculomegaly and neuroimmune alterations in Hoatz-deficient mice.Fluids and barriers of the CNS · 2026Article
- Fetal mri of obstructive hydrocephalus: a review proposing a surgical etiology-based approach.Neuroradiology · 2026Review
- De NovoHuman mutation · 2026Article
- Hydrocephalus in Connection to Genetic Mutation in Cranial Neural Crest Cells.Orthodontics & craniofacial research · 2025Review
- Preclinical evaluation of antisense oligonucleotide therapy in a mouse model ofbioRxiv : the preprint server for biology · 2025Article
- The RNA-binding protein TRIM71 is essential for hearing in humans and mice and times auditory sensory organ development.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Age-dependent brain responses to mechanical stress determine resilience in a chronic lymphatic drainage impairment model.The Journal of clinical investigation · 2025Article
- Article
- Expression of α-smooth muscle actin in the lateral ventricle wall of spontaneous hydrocephalus animals.The Journal of veterinary medical science · 2025Article
- Cell-specific expression biases in human cortex of genes associated with neurodevelopmental disorders.Scientific reports · 2025Article
- Molecular hallmarks of hydrocephalus.Science translational medicine · 2025Review
- Neural stem cell changes and spatial distribution of AQP4 expression in a fetal goat model of obstructive hydrocephalus.IBRO neuroscience reports · 2025Article
- Precision medicine in the pediatric and neonatal intensive care units through genomics.Current opinion in pediatrics · 2025Review
- De novo variants disrupt an LDB1-regulated transcriptional network in congenital ventriculomegaly.Brain : a journal of neurology · 2025Article
- Impaired primitive erythropoiesis and defective vascular development in Trim71-KO embryos.Life science alliance · 2025Article
- Perturbed cell fate decision by schizophrenia-associated AS3MTScience advances · 2025Article
- IFN-γ signaling links ventriculomegaly to choroid plexus and ependyma dysfunction following maternal immune activation.Journal of neuroinflammation · 2025Article
- Research priorities for non-invasive therapies to improve hydrocephalus outcomes.Fluids and barriers of the CNS · 2025Review
- PTEN mutations impair CSF dynamics and cortical networks by dysregulating periventricular neural progenitors.Nature neuroscience · 2025Article
- Multimodal insights into adult neurogenesis: An integrative review of multi-omics approaches.Heliyon · 2025Review
3 more citing papers are in PubMed but not listed here.
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Authors and funding
67 authors at 14 institutions in 3 countries.
Phan Q Duy *Department of Neuroscience and Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-4513-7348
Stefan C Weise *Molecular Immunology and Cell Biology, Life & Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany.
Claudia MariniInstitute for Cell Biology and Neurobiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Xiao-Jun LiSolomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Dan LiangDepartment of Neuroscience and Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, CT, USA.
Peter J DahlMicrobial Sciences Institute, Yale University, West Haven, CT, USA.
Shaojie MaDepartment of Neuroscience and Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-8782-3047
Ana SpajicDepartment of Neuroscience and Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, CT, USA.
Weilai DongLaboratory of Human Genetics and Genomics, The Rockefeller University, New York, NY, USA.ORCID http://orcid.org/0000-0002-8376-1758
Jane JuusolaGeneDx, Gaithersburg, MD, USA.
Emre KiziltugDepartment of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA.
Adam J KundishoraDepartment of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA.
Sunil KoundalDepartment of Anesthesiology, Yale University School of Medicine, New Haven, CT, USA.
Maysam Z PedramDepartment of Anesthesiology, Yale University School of Medicine, New Haven, CT, USA.
Lucia A Torres-FernándezMolecular Immunology and Cell Biology, Life & Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany.
Kristian HändlerSystems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany.
Elena De DomenicoSystems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany.ORCID http://orcid.org/0000-0003-0336-8284
Matthias BeckerSystems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany.ORCID http://orcid.org/0000-0002-7120-4508
Thomas UlasSystems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany.
Stefan A JuranekDepartment of Oncology, Hematology and Rheumatology, University Hospital Bonn, Bonn, Germany.ORCID http://orcid.org/0000-0002-9136-4461
Elisa CuevasStem Cells and Regenerative Medicine Section, University College London Great Ormond Street Institute of Child Health, London, UK.
Le Thi HaoDepartment of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA.
Bettina JuxMolecular Immunology and Cell Biology, Life & Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany.
André M M SousaDepartment of Neuroscience and Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, CT, USA.
Fuchen LiuDepartment of Neuroscience and Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0003-0380-850X
Suel-Kee KimDepartment of Neuroscience and Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0003-0240-9304
Mingfeng LiDepartment of Neuroscience and Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-7959-6008
Yiying YangYale Stem Cell Center, Yale University School of Medicine, New Haven, CT, USA.
Yutaka TakeoDepartment of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA.
Alvaro DuqueDepartment of Neuroscience and Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-5086-5438
Carol Nelson-WilliamsDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0003-0768-4751
Yonghyun HaDepartment of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-7845-0090
Kartiga SelvaganesanDepartment of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT, USA.
Stephanie M RobertDepartment of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA.
Amrita K SinghDepartment of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA.
Garrett AllingtonDepartment of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA.
Charuta G FureyDepartment of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA.
Andrew T TimberlakeDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-8926-9692
Benjamin C ReevesDepartment of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-5924-6991
Hannah SmithDepartment of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA.
Ashley DunbarDepartment of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA.
Tyrone DeSpenzaDepartment of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA.
June GotoDivision of Pediatric Neurosurgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.ORCID http://orcid.org/0000-0002-4000-9750
Arnaud MarlierDepartment of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA.
Andres Moreno-De-LucaDepartment of Radiology, Autism & Developmental Medicine Institute, Genomic Medicine Institute, Geisinger, Danville, PA, USA.ORCID http://orcid.org/0000-0002-2732-4043
Xin YuDepartment of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
William E ButlerDepartment of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Bob S CarterDepartment of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Evelyn M R LakeDepartment of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0001-8255-8013
R Todd ConstableDepartment of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0001-5661-9521
Pasko RakicDepartment of Neuroscience and Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-6963-0508
Haifan LinYale Stem Cell Center, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-5374-9491
Engin DenizDepartment of Pediatrics, Yale University School of Medicine, New Haven, CT, USA.
Helene BenvenisteDepartment of Anesthesiology, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-2887-6667
Nikhil S MalvankarMicrobial Sciences Institute, Yale University, West Haven, CT, USA.ORCID http://orcid.org/0000-0001-5611-6633
Juvianee I Estrada-VerasHenry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-2372-0372
Christopher A WalshDivision of Genetics and Genomics, Manton Center for Orphan Disease Research, Department of Pediatrics, and Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0002-0156-2238
Seth L AlperBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-6228-2512
Joachim L SchultzeSystems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany.ORCID http://orcid.org/0000-0003-2812-9853
Katrin PaeschkeDepartment of Oncology, Hematology and Rheumatology, University Hospital Bonn, Bonn, Germany.
Angelika DoetzlhoferSolomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-7424-2112
F Gregory WulczynInstitute for Cell Biology and Neurobiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.ORCID http://orcid.org/0000-0001-9850-2444
Sheng Chih JinDepartment of Genetics, Washington University School of Medicine, St. Louis, MO, USA.
Richard P LiftonLaboratory of Human Genetics and Genomics, The Rockefeller University, New York, NY, USA.
Nenad SestanDepartment of Neuroscience and Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0003-0966-9619
Waldemar KolanusMolecular Immunology and Cell Biology, Life & Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany.ORCID http://orcid.org/0000-0003-1325-9444
Kristopher T KahleDepartment of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. kahle.kristopher@mgh.harvard.edu.ORCID http://orcid.org/0000-0002-5922-7547
Yale University · USUniversity of Bonn · DEBroad Institute · USHarvard University · USHumboldt-Universität zu Berlin · DEJohns Hopkins University · USRockefeller University · USUniversity Hospital Bonn · DEYale Cancer Center · USAutism & Developmental Medicine Institute · USCincinnati Children's Hospital Medical Center · USGreat Ormond Street Hospital · GBHenry M. Jackson Foundation · USWashington University in St. Louis · US
Funding
Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9MMedical Scientist Training ProgramT32GM136651 · NIGMS · YALE UNIVERSITY · PI BARBARA I KAZMIERCZAK · 2020 to 2026
$16.5MHUMAN EPILEPSY GENETICS--NEURONAL MIGRATION DISORDERSR01NS035129 · NINDS · BOSTON CHILDREN'S HOSPITAL · PI WALSH, CHRISTOPHER A. · 1997 to 2023
$9.5MGenetic Analysis and Manipulation Core (GAEC)P50HD105351 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI SCOTT Loren POMEROY, MUSTAFA SAHIN · 2021 to 2026
$9.4MOrigin of Cortical Species-specific Distinctions.R01DA023999 · NIDA · YALE UNIVERSITY · PI RAKIC, PASKO · 2008 to 2019
$7.9MOrigin of Cortical Species-specific DistinctionsR37DA023999 · NIDA · YALE UNIVERSITY · PI PASKO RAKIC · 2020 to 2026
$5.6MYale Macaque Brain ResourceR01MH113257 · NIMH · YALE UNIVERSITY · PI Alvaro Duque · 2017 to 2026
$4.3MInvestigating the Thalamic Regulation of Neuro-Glio-Vascular Restoration Underlying Acute Coma Recovery with Multi-Modal fMRI in a Brainstem Coma Rodent ModelR01NS122904 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI YU, XIN · 2021 to 2025
$3.2MTargeting bacterial infections by imaging electrical interactions between host surface pathogensDP2AI138259 · NIAID · YALE UNIVERSITY · PI MALVANKAR, NIKHIL · 2017 to 2017
$2.5MHuman Genetics and Molecular Mechanisms of Congenital HydrocephalusR01NS111029 · NINDS · YALE UNIVERSITY · PI DENIZ, ENGIN, JIN, SHENG CHIH · 2020 to 2024
$2.5MAnalysis of Congenital Hydrocephalus Genes in XenopusR01NS127879 · NINDS · YALE UNIVERSITY · PI ENGIN DENIZ · 2022 to 2026
$2.3MDevelop a multi-modal cross-scale fMRI platform with laminar-specific cellular recordings through multi-channel tapered photonic crystal fiber arrayRF1NS113278 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI YU, XIN · 2019 to 2019
$2.0MNCATS NIH HHS UL1 TR001863NHLBI NIH HHS K99 HL143036NHLBI NIH HHS R00 HL143036NIAID NIH HHS DP2 AI138259NICHD NIH HHS F30 HD106694NICHD NIH HHS P50 HD105351NIDA NIH HHS R01 DA023999NIDA NIH HHS R37 DA023999NIGMS NIH HHS T32 GM136651NIMH NIH HHS R01 MH113257NIMH NIH HHS S10 MH124733NINDS NIH HHS R01 NS035129NINDS NIH HHS R01 NS111029NINDS NIH HHS R01 NS122904NINDS NIH HHS R01 NS127879NINDS NIH HHS R21 NS116484NINDS NIH HHS R21 NS121642NINDS NIH HHS RF1 NS113278
Abstract
Hydrocephalus, characterized by cerebral ventricular dilatation, is routinely attributed to primary defects in cerebrospinal fluid (CSF) homeostasis. This fosters CSF shunting as the leading reason for brain surgery in children despite considerable disease heterogeneity. In this study, by integrating human brain transcriptomics with whole-exome sequencing of 483 patients with congenital hydrocephalus (CH), we found convergence of CH risk genes in embryonic neuroepithelial stem cells. Of all CH risk genes, TRIM71/lin-41 harbors the most de novo mutations and is most specifically expressed in neuroepithelial cells. Mice harboring neuroepithelial cell-specific Trim71 deletion or CH-specific Trim71 mutation exhibit prenatal hydrocephalus. CH mutations disrupt TRIM71 binding to its RNA targets, causing premature neuroepithelial cell differentiation and reduced neurogenesis. Cortical hypoplasia leads to a hypercompliant cortex and secondary ventricular enlargement without primary defects in CSF circulation. These data highlight the importance of precisely regulated neuroepithelial cell fate for normal brain-CSF biomechanics and support a clinically relevant neuroprogenitor-based paradigm of CH.
Indexed as
HydrocephalusAnimalsBiomechanical PhenomenaBrainCerebrospinal FluidExome SequencingHumansMiceNeurogenesisTripartite Motif ProteinsUbiquitin-Protein LigasesTRIM71 protein, humanTripartite Motif ProteinsUbiquitin-Protein Ligases
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