ArticleHuman molecular genetics2013
The functional genetic link of NLGN4X knockdown and neurodevelopment in neural stem cells.
Article in Human molecular genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- Insertion of rare autism variants in synaptic genes induce novel behavioral phenotypes inbioRxiv : the preprint server for biology · 2025Article
- Human stem cell-based models to study synaptic dysfunction and cognition in schizophrenia: A narrative review.Schizophrenia research · 2024Review
- Late stage melanoma is hallmarked by low NLGN4X expression leading to HIF1A accumulation.British journal of cancer · 2024Article
- Fluid Flow Stimulation Modulates Expression of S100 Genes in Normal Breast Epithelium and Breast Cancer.Cellular and molecular bioengineering · 2022Article
- Genome-Wide Detection of Copy Number Variations and Evaluation of Candidate Copy Number Polymorphism Genes Associated With Complex Traits of Pigs.Frontiers in veterinary science · 2022Article
- Copy number variation characterization and possible candidate genes in miscarriage and stillbirth by next-generation sequencing analysis.The journal of gene medicine · 2021Article
- [Proteolytic cleavage of neuroligins and functions of their cleavage products].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2020Review
- Novel Microdeletion in the X Chromosome Leads to Kallmann Syndrome, Ichthyosis, Obesity, and Strabismus.Frontiers in genetics · 2020Article
- Elevated Plasma X-Linked Neuroligin 4 Expression Is Associated with Autism Spectrum Disorder.Medical principles and practice : international journal of the Kuwait University, Health Science Centre · 2020Article
- Uncovering the Functional Link BetweenFrontiers in neuroanatomy · 2019Article
- Glycosphingolipid metabolic reprogramming drives neural differentiation.The EMBO journal · 2018Article
- Psychosis Risk Candidate ZNF804A Localizes to Synapses and Regulates Neurite Formation and Dendritic Spine Structure.Biological psychiatry · 2017Article
- Genome-wide association study for feed efficiency and growth traits in U.S. beef cattle.BMC genomics · 2017Article
- Emerging Synaptic Molecules as Candidates in the Etiology of Neurological Disorders.Neural plasticity · 2017Review
- Spatial sexual dimorphism of X and Y homolog gene expression in the human central nervous system during early male development.Biology of sex differences · 2016Article
- Uncovering obsessive-compulsive disorder risk genes in a pediatric cohort by high-resolution analysis of copy number variation.Journal of neurodevelopmental disorders · 2016Article
- Single- and Bayesian Multi-Marker Genome-Wide Association for Haematological Parameters in Pigs.PloS one · 2016Article
- A molecular model for neurodevelopmental disorders.Translational psychiatry · 2015Article
- Genetics studies indicate that neural induction and early neuronal maturation are disturbed in autism.Frontiers in cellular neuroscience · 2014Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Genetic mutations in NLGN4X (neuroligin 4), including point mutations and copy number variants (CNVs), have been associated with susceptibility to autism spectrum disorders (ASDs). However, it is unclear how mutations in NLGN4X result in neurodevelopmental defects. Here, we used neural stem cells (NSCs) as in vitro models to explore the impacts of NLGN4X knockdown on neurodevelopment. Using two shRNAmir-based vectors targeting NLGN4X and one control shRNAmir vector, we modulated NLGN4X expression and differentiated these NSCs into mature neurons. We monitored the neurodevelopmental process at Weeks 0, 0.5, 1, 2, 4 and 6, based on morphological analysis and whole-genome gene expression profiling. At the cellular level, in NSCs with NLGN4X knockdown, we observed increasingly delayed neuronal development and compromised neurite formation, starting from Week 2 through Week 6 post differentiation. At the molecular level, we identified multiple pathways, such as neurogenesis, neuron differentiation and muscle development, which are increasingly disturbed in cells with NLGN4X knockdown. Notably, several postsynaptic genes, including DLG4, NLGN1 and NLGN3, also have decreased expression. Based on in vitro models, NLGN4X knockdown directly impacts neurodevelopmental process during the formation of neurons and their connections. Our functional genomics study highlights the utility of NSCs models in understanding the functional roles of CNVs in affecting neurodevelopment and 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.