ArticlePloS one2014
Autism associated gene, engrailed2, and flanking gene levels are altered in post-mortem cerebellum.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Pooled it
- The Role of Serotonin in Brain Development: From Molecular Pathways to Neurodevelopmental Risk.Cellular and molecular neurobiology · 2026Review
- Autism Spectrum Disorder: The Cerebellum, Genes, and Pathways.Neurology international · 2025Review
- Article
- The role of canopy family proteins: biological mechanism and disease function.Molecular biology reports · 2025Review
- Engrailed-2 and inflammation convergently and independently impinge on cerebellar Purkinje cell differentiation.Journal of neuroinflammation · 2024Article
- The role of Smo-Shh/Gli signaling activation in the prevention of neurological and ageing disorders.Biogerontology · 2023Review
- Improvement of the Clinical and Psychological Profile of Patients with Autism after Methylcobalamin Syrup Administration.Nutrients · 2022Article
- Smoothened receptor signaling regulates the developmental shift of GABA polarity in rat somatosensory cortex.Journal of cell science · 2020Article
- Impaired neurodevelopmental pathways in autism spectrum disorder: a review of signaling mechanisms and crosstalk.Journal of neurodevelopmental disorders · 2019Review
- Aberrant Somatosensory Processing and Connectivity in Mice LackingThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Sensory Abnormalities in Autism Spectrum Disorders: A Focus on the Tactile Domain, From Genetic Mouse Models to the Clinic.Frontiers in psychiatry · 2019Review
- Time Course of Changes in Peripheral Blood Gene Expression During Medication Treatment for Major Depressive Disorder.Frontiers in genetics · 2019Article
- Altered salt taste response and increased tongue epithelium Scnna1 expression in adult Engrailed-2 null mice.Physiology & behavior · 2018Article
- Insulin receptor in the brain: Mechanisms of activation and the role in the CNS pathology and treatment.CNS neuroscience & therapeutics · 2018Review
- Clinical Phenotypes Associated to Engrailed 2 Gene Alterations in a Series of Neuropediatric Patients.Frontiers in neuroanatomy · 2018Article
- Selection of Suitable Reference Genes for Analysis of Salivary Transcriptome in Non-Syndromic Autistic Male Children.International journal of molecular sciences · 2016Article
- Comparative Gene Expression Analysis of Two Mouse Models of Autism: Transcriptome Profiling of the BTBR and En2 (-/-) Hippocampus.Frontiers in neuroscience · 2016Article
- Engrailed-2 (En2) deletion produces multiple neurodevelopmental defects in monoamine systems, forebrain structures and neurogenesis and behavior.Human molecular genetics · 2015Article
- Autism spectrum disorders and neuropathology of the cerebellum.Frontiers in neuroscience · 2015Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundPrevious genetic studies demonstrated association between the transcription factor engrailed2 (EN2) and Autism Spectrum Disorder (ASD). Subsequent molecular analysis determined that the EN2 ASD-associated haplotype (rs1861972-rs1861973 A-C) functions as a transcriptional activator to increase gene expression. EN2 is flanked by 5 genes, serotonin receptor5a (HTR5A), insulin induced gene1 (INSIG1), canopy1 homolog (CNPY1), RNA binding motif protein33 (RBM33), and sonic hedgehog (SHH). These flanking genes are co-expressed with EN2 during development and coordinate similar developmental processes. To investigate if mRNA levels for these genes are altered in individuals with autism, post-mortem analysis was performed.
methodsqRT-PCR quantified mRNA levels for EN2 and the 5 flanking genes in 78 post-mortem cerebellar samples. mRNA levels were correlated with both affection status and rs1861972-rs1861973 genotype. Molecular analysis investigated whether EN2 regulates flanking gene expression.
resultsEN2 levels are increased in affected A-C/G-T individuals (p = .0077). Affected individuals also display a significant increase in SHH and a decrease in INSIG1 levels. Rs1861972-rs1861973 genotype is correlated with significant increases for SHH (A-C/G-T) and CNPY1 (G-T/G-T) levels. Human cell line over-expression and knock-down as well as mouse knock-out analysis are consistent with EN2 and SHH being co-regulated, which provides a possible mechanism for increased SHH post-mortem levels.
conclusionsEN2 levels are increased in affected individuals with an A-C/G-T genotype, supporting EN2 as an ASD susceptibility gene. SHH, CNPY1, and INSIG1 levels are also significantly altered depending upon affection status or rs1861972-rs1861973 genotype. Increased EN2 levels likely contribute to elevated SHH expression observed in the post-mortem samples.
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Registered trials
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