ArticleDevelopment (Cambridge, England)2010
An SNP in an ultraconserved regulatory element affects Dlx5/Dlx6 regulation in the forebrain.
Article in Development (Cambridge, England), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- Early developmental gene enhancers affect subcortical volumes in the adult human brain.Human brain mapping · 2016Pooled it
- ASD mutations in the ciliary gene CEP41 impact development of projection neurons and interneurons in a human cortical organoid model.Molecular psychiatry · 2026Article
- The mutational landscape and functional effects of noncoding ultraconserved elements in human cancers.Science advances · 2025Article
- Functional associations of evolutionarily recent human genes exhibit sensitivity to the 3D genome landscape and disease.bioRxiv : the preprint server for biology · 2024Article
- Article
- DLX genes and proteins in mammalian forebrain development.Development (Cambridge, England) · 2024Review
- Article
- GC-biased gene conversion drives accelerated evolution of ultraconserved elements in mammalian and avian genomes.Genome research · 2023Article
- Transcription factor TFII-I fine tunes innate properties of B lymphocytes.Frontiers in immunology · 2023Article
- Article
- DLX5/6 GABAergic Expression Affects Social Vocalization: Implications for Human Evolution.Molecular biology and evolution · 2021Article
- Williams syndrome.Nature reviews. Disease primers · 2021Review
- Single-Cell Transcriptomics Supports a Role ofInternational journal of molecular sciences · 2021Review
- Increased Sociability in Mice Lacking IntergenicFrontiers in neuroscience · 2021Article
- Association of GTF2I gene polymorphisms with renal involvement of systemic lupus erythematosus in a Chinese population.Medicine · 2019Observational
- Dlx1 and Dlx2 Promote Interneuron GABA Synthesis, Synaptogenesis, and Dendritogenesis.Cerebral cortex (New York, N.Y. : 1991) · 2018Article
- Ultraconserved Elements Occupy Specific Arenas of Three-Dimensional Mammalian Genome Organization.Cell reports · 2018Article
- Toward the Language Oscillogenome.Frontiers in psychology · 2018Article
- Role of Splice Variants of Gtf2i, a Transcription Factor Localizing at Postsynaptic Sites, and Its Relation to Neuropsychiatric Diseases.International journal of molecular sciences · 2017Review
- CRISPR/Cas9-mediated heterozygous knockout of the autism gene CHD8 and characterization of its transcriptional networks in cerebral organoids derived from iPS cells.Molecular autism · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Dlx homeobox genes play a crucial role in the migration and differentiation of the subpallial precursor cells that give rise to various subtypes of gamma-aminobutyric acid (GABA)-expressing neurons of the forebrain, including local-circuit cortical interneurons. Aberrant development of GABAergic interneurons has been linked to several neurodevelopmental disorders, including epilepsy, schizophrenia, Rett syndrome and autism. Here, we report in mice that a single-nucleotide polymorphism (SNP) found in an autistic proband falls within a functional protein binding site in an ultraconserved cis-regulatory element. This element, I56i, is involved in regulating Dlx5/Dlx6 homeobox gene expression in the developing forebrain. We show that the SNP results in reduced I56i activity, predominantly in the medial and caudal ganglionic eminences and in streams of neurons tangentially migrating to the cortex. Reduced activity is also observed in GABAergic interneurons of the adult somatosensory cortex. The SNP affects the affinity of Dlx proteins for their binding site in vitro and reduces the transcriptional activation of the enhancer by Dlx proteins. Affinity purification using I56i sequences led to the identification of a novel regulator of Dlx gene expression, general transcription factor 2 I (Gtf2i), which is among the genes most often deleted in Williams-Beuren syndrome, a neurodevelopmental disorder. This study illustrates the clear functional consequences of a single nucleotide variation in an ultraconserved non-coding sequence in the context of developmental abnormalities associated with disease.
Indexed as
Identifiers
What OpenQuestion holds
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.