ArticlePloS one2013
Functional impacts of NRXN1 knockdown on neurodevelopment in stem cell models.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 82 citations in OpenAlex.
- Neurexin dysfunction in neurodevelopmental and neuropsychiatric disorders: a PRIMSA-based systematic review through iPSC and animal models.Frontiers in behavioral neuroscience · 2024Pooled it
- Evidence of neurocognitive and resting state functional connectivity differences in carriers of NRXN1 deletions.Journal of neurodevelopmental disorders · 2025Article
- Psychiatric Genomics 2025: State of the Art and the Path Forward.The Psychiatric clinics of North America · 2025Review
- Alpha-neurexins in health and disease.Frontiers in molecular neuroscience · 2025Review
- Endophenotype 2.0: updated definitions and criteria for endophenotypes of psychiatric disorders, incorporating new technologies and findings.Translational psychiatry · 2024Review
- Stem cell engineering approaches for investigating glial cues in central nervous system disorders.Current opinion in biotechnology · 2024Review
- Multiplexing of TMT labeling reveals folate-deficient diet-specific proteome changes in NTDs.Frontiers in cell and developmental biology · 2024Article
- Review
- Schizophrenia-associated NRXN1 deletions induce developmental-timing- and cell-type-specific vulnerabilities in human brain organoids.Nature communications · 2023Article
- Evaluating the mouse neural precursor line, SN4741, as a suitable proxy for midbrain dopaminergic neurons.BMC genomics · 2023Article
- Evaluating the mouse neural precursor line, SN4741, as a suitable proxy for midbrain dopaminergic neurons.Research square · 2023Article
- Evaluating the mouse neural precursor line, SN4741, as a suitable proxy for midbrain dopaminergic neurons.bioRxiv : the preprint server for biology · 2023Article
- Single-cell RNA sequencing of neurofibromas reveals a tumor microenvironment favorable for neural regeneration and immune suppression in a neurofibromatosis type 1 porcine model.Frontiers in oncology · 2023Article
- Distinct gene expression in demyelinated white and grey matter areas of patients with multiple sclerosis.Brain communications · 2022Article
- Neurons and Astrocytes Elicit Brain Region Specific Transcriptional Responses to Prion Disease in the Murine CA1 and Thalamus.Frontiers in neuroscience · 2022Article
- LncRNA expression in idiopathic achalasia: New insight and preliminary exploration into pathogenesis.Open medicine (Warsaw, Poland) · 2022Article
- The Prevailing Role of Topoisomerase 2 Beta and its Associated Genes in Neurons.Molecular neurobiology · 2021Review
- RNA sequencing and functional studies of patient-derived cells reveal that neurexin-1 and regulators of this pathway are associated with poor outcomes in Ewing sarcoma.Cellular oncology (Dordrecht, Netherlands) · 2021Article
- Neurexins in autism and schizophrenia-a review of patient mutations, mouse models and potential future directions.Molecular psychiatry · 2021Review
- miR-196a-2 Promotes Malignant Progression of Thyroid Carcinoma by Targeting NRXN1.Computational and mathematical methods in medicine · 2021Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Exonic deletions in NRXN1 have been associated with several neurodevelopmental disorders, including autism, schizophrenia and developmental delay. However, the molecular mechanism by which NRXN1 deletions impact neurodevelopment remains unclear. Here we used human induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs) as models to investigate the functional impacts of NRXN1 knockdown. We first generated hiPSCs from skin fibroblasts and differentiated them into neural stem cells (NSCs). We reduced NRXN1 expression in NSCs via a controlled shRNAmir-based knockdown system during differentiation, and monitored the transcriptome alteration by RNA-Seq and quantitative PCR at several time points. Interestingly, half reduction of NRXN1 expression resulted in changes of expression levels for the cell adhesion pathway (20 genes, P = 2.8×10(-6)) and neuron differentiation pathway (13 genes, P = 2.1×10(-4)), implicating that single-gene perturbation can impact biological networks important for neurodevelopment. Furthermore, astrocyte marker GFAP was significantly reduced in a time dependent manner that correlated with NRXN1 reduction. This observation was reproduced in both hiPSCs and hESCs. In summary, based on in vitro models, NRXN1 deletions impact several biological processes during neurodevelopment, including synaptic adhesion and neuron differentiation. Our study highlights the utility of stem cell models in understanding the functional roles of copy number variations (CNVs) in conferring susceptibility to neurodevelopmental diseases.
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Registered trials
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.